Systems and methods for tracking an intrabody catheter

ABSTRACT

There is provided a computerized method of tracking a position of an intra-body catheter, comprising: physically tracking coordinates of the position of a distal portion of a physical catheter within the physical body portion of the patient according to physically applied plurality of electrical fields within the body portion and measurements of the plurality of electrical fields performed by a plurality of physical electrodes at a distal portion of the physical catheter; registering the physically tracked coordinates with simulated coordinates generated according to a simulation of a simulated catheter within a simulation of the body of the patient, to identify differences between physically tracked location coordinates and the simulation coordinates; correcting the physically tracked location coordinates according to the registered simulation coordinates; and providing the corrected physically tracked location coordinates for presentation.

RELATED APPLICATIONS

This application is a National Phase of PCT Patent Application No.PCT/IB2016/052687 having International filing date of May 11, 2016,which claims the benefit of priority under 35 USC § 119(e) of U.S.Provisional Patent Application Nos. 62/160,080 filed on May 12, 2015,62/291,065 filed on Feb. 4, 2016, and 62/304,455 filed on Mar. 7, 2016.The contents of the above applications are all incorporated by referenceas if fully set forth herein in their entirety.

PCT Patent Application No. PCT/IB2016/052687 is also related to PCTPatent Application Nos. PCT/IB2016/052690, titled “LESION ASSESSMENT BYDIELECTRIC PROPERTY ANALYSIS”, PCT/IB2016/052688 titled “CALCULATION OFAN ABLATION PLAN”, PCT/IB2016/052692 titled “FIDUCIAL MARKING FORIMAGE-ELECTROMAGNETIC FIELD REGISTRATION”, and PCT/IB2016/052686 titled“CONTACT QUALITY ASSESSMENT BY DIELECTRIC PROPERTY ANALYSIS”, all havingthe International filing date of May 11, 2016.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to systemsand methods for tracking intrabody catheters and, more particularly, butnot exclusively, to systems and methods for non-fluoroscopic tracking ofintrabody catheters.

Systems and methods have been developed for non-fluoroscopic tracking ofintrabody catheters, for example, for tracking a catheter during acardiac procedure, such as intra-cardiac ablation.

Frederik H. M. Wittkampf, in U.S. Pat. No. 5,983,126 describes “A systemand method are provided for catheter location mapping, and relatedprocedures. Three substantially orthogonal alternating signals areapplied through the patient, directed substantially toward the area ofinterest to be mapped, such as patient's heart. The currents arepreferably constant current pulses, of a frequency and magnitude toavoid disruption with ECG recordings. A catheter is equipped with atleast a measuring electrode, which for cardiac procedures is positionedat various locations either against the patient's heart wall, or withina coronary vein or artery. A voltage is sensed between the catheter tipand a reference electrode, preferably a surface electrode on thepatient, which voltage signal has components corresponding to the threeorthogonal applied current signals. Three processing channels are usedto separate out the three components as x, y and z signals, from whichcalculations are made for determination of the three-dimensionallocation of the catheter tip within the body.”

SUMMARY OF THE INVENTION

According to an aspect of some embodiments of the present inventionthere is provided a computerized method of tracking a position of anintra-body catheter, comprising: physically tracking coordinates of theposition of a distal portion of a physical catheter within the physicalbody portion of the patient according to physically applied plurality ofelectrical fields within the body portion and measurements of theplurality of electrical fields performed by a plurality of physicalelectrodes at a distal portion of the physical catheter; registering thephysically tracked coordinates with simulated coordinates generatedaccording to a simulation of a simulated catheter within a simulation ofthe body of the patient, to identify differences between physicallytracked location coordinates and the simulation coordinates; correctingthe physically tracked location coordinates according to the registeredsimulation coordinates; and providing the corrected physically trackedlocation coordinates for presentation.

Optionally, the method further comprises providing a dataset of a bodyportion of a patient including anatomical imaging data of the patient,and at least one dielectric parameter value corresponding to one or moreof different tissues of the anatomical imaging data, wherein the atleast one dielectric parameter value represents an initial estimatedvalue; and generating the simulation that tracks coordinates of aposition of the simulated catheter within the dataset representing thebody portion according to simulated application of a plurality ofelectrical fields within the body portion and measurements of theplurality of electrical fields performed by a plurality of electrodes ata distal portion of the catheter. Optionally, the at least onedielectric parameter value includes an impedance value of the respectivetissue. Optionally, the dataset includes at least one thermal parametercorresponding to the one or more of different tissues of the anatomicalimaging data, wherein the at least one thermal parameter value affectsthe at least one dielectric parameter value, and wherein generatingcomprises generating the simulation according to simulated values of theat least one thermal parameter.

Optionally, the simulation includes a simulation of a plurality ofextra-body electrodes that generate the plurality of electrical fields.Optionally, the method further comprises executing the simulation byvarying at least one parameter of at least one of the extra-bodyelectrodes, estimating an inaccuracy in simulation coordinates inproximity to a target tissue, repeating the simulation and theestimating by varying at least one of parameters, and selecting the atleast one varied parameter to reduce the inaccuracy. Optionally, the atleast one parameter is selected from the group consisting of: extra-bodyelectrode location, size of transmitting extra-body electrode surfacearea, geometry of transmitting extra-body electrode surface area,electric field strength, electric current amplitude, and frequency ofelectric current.

Optionally, the simulation includes a simulation of at least oneparameter that modifies the measurements of the plurality of electricalfields and/or modifies a dielectric measurement of tissue, and furthercomprising executing the simulation by varying the at least oneparameter, estimating an inaccuracy in simulation coordinates inproximity to a target tissue, repeating the simulation and theestimating by varying at least one of the at least one parameters, andselecting the at least one varied parameter to reduce the inaccuracy.Optionally, the at least one parameter is selected from the groupconsisting of: location of multiple catheters, effect of drugs, effectof disease, effect of pre-applied treatments, effect of mechanical forceapplied to tissues, effect of applying a thermal intervention, effect oftransmitting signal(s) into the body, and effect of transmittingsignal(s) out of the body.

Optionally, the method further comprises injecting a predefined signalto the plurality of extra-body electrodes that generate the plurality ofelectrical fields, using the injected signal to analyze the effectsbefore, during, and/or after an ablation procedure on measurements ofthe plurality of electrical fields, and correcting the physicallytracked location coordinates according to the analysis.

Optionally, the method further comprises executing the simulationincluding another simulated catheter having a plurality of electrodes ata distal portion thereof, estimating an inaccuracy in simulationcoordinates in proximity to a target tissue for each simulated catheterrelated to cross-talk, repeating the simulation and the estimating byvarying at least one of the simulated catheters, and selecting the atleast one varied catheter to reduce the inaccuracy related tocross-talk.

Optionally, registering further comprises calibrating the simulationlocation coordinates according to a defined anatomical and physicallocation of the distal end portion of the physical catheter.

Optionally, the simulation includes determining for tissue being ablatedaccording to the corrected physically tracked location coordinates, atleast one of: a power loss density (PLD) pattern, a gasificationtransition, and a temperature pattern.

Optionally, the method further comprises receiving a real-timemeasurement of at least one dielectric parameter of at least oneintra-body tissue; generating an updated simulation by updating theinitial estimated value of the at least one dielectric parameter valuewith the real-time measurement; and repeating the registering and thecorrecting. Optionally, the registering and the correcting are repeateduntil a stop condition is met, wherein the stop condition is identifiedby matching of a predefined signal template indicative of achievement ofa desired ablation pattern to sensed signals and/or measurements.Optionally, the matched predefined signal template is indicative of atleast one of: tissue coagulation, tissue edema, transmural ablation,continuous ablation line, safety indicator, and procedure effectivenessindicator.

Optionally, the at least one dielectric parameter is at least one ofimpedance and conductivity, and the at least one intra-body tissue is atleast one of blood and myocardium. Optionally, the generating, theregistering, and the correcting are performed for a sub-volume thatincludes a target tissue in near proximity to the distal end of thephysical catheter. Alternatively or additionally, the generating, theregistering, and the correcting are iteratively performed withdecreasing volumes of the sub-volume as the distance between the distalend of the physical catheter and the target tissue decreases.Optionally, the iterations are performed to achieve an accuracy of about+/−1 millimeter of the corrected physically tracked coordinates.

Optionally, the method further comprises measuring a thickness of atissue including a target tissue according to a dataset includinganatomical image data of the patient; iteratively receiving, from atleast one electrode of the physical catheter, at least one measurementof at least one dielectric parameter of tissue in proximity to thetarget tissue, the at least one measurement performed before an ablationof the target tissue, during the ablation, and after the ablation; anditeratively correlating the measured thickness with the received atleast one electrical parameter to estimate at least one of a lesionvolume and a lesion depth.

Optionally, the simulation includes a simulated ablation of the targettissue according to a simulated optimal contact force between the distalend portion of the simulated catheter and tissue in proximity to thetarget tissue, and further comprising correlating the at least onedielectric parameter to estimate a quality of the contact force relativeto the simulated optimal contact force. Optionally, the estimatedquality of the contact force is selected from the group consisting of:suboptimal contact force, optimal contact force, and excessive contactforce. Optionally, the simulation is according to at least one ablationparameter. Optionally, the at least one measurement is performed in atleast two frequencies.

Optionally, the method further comprises iteratively receiving, from atleast one electrode of the physical catheter during the physicallytracking, at least one measurement of a dielectric parameter of tissuein proximity to a target tissue, the at least one measurement performeda plurality of locations in proximity to the target tissue; analyzingthe at least measurement associated with each of the plurality oflocations to identify an electrical tissue signature indicative of atleast one fibrotic tissue region; and mapping the at least one fibrotictissue region to a dataset including anatomical image data of thepatient, for display.

Optionally, the method further comprises analyzing a trajectory of thephysically tracked coordinates of the position of a distal portion of aphysical catheter over a time range including at least one cardiaccycle; and estimating a quality of contact between the distal portion ofthe physical catheter and a pulsating tissue portion according to theanalyzed trajectory. Optionally, analyzing further comprises at leastone of measuring and simulating motion of the pulsating tissue over thetime range; and correlating the physically tracked coordinates of theposition of the distal portion with the motion of the pulsating tissue.Optionally, measuring of the pulsating tissue is performed according togating of a real-time ECG measurement.

Optionally, the body portion includes a heart and the simulationincludes tracking coordinates of navigation of the simulated catheterwithin the heart for an intra-cardiac ablation procedure.

Optionally, the physically tracking is based on impedance based mappingtechniques.

Optionally, the method further comprises receiving, from at least oneelectrode of the physical catheter contacting a tissue during thephysically tracking, at least one measurement of a dielectric parameterof tissue in proximity to a target tissue; applying a trained machinelearning method to the at least one measurement to generate a correlatedestimated applied force between the physical catheter and the contactingtissue; wherein the trained machine learning method is based on a fittedcorrelation between multiple impedance values measured at multiplelocations of a sample tissue similar to the contacting tissue.Optionally, the estimated applied contact force is selected from thegroup consisting of: suboptimal contact force, optimal contact force,and excessive contact force.

According to an aspect of some embodiments of the present inventionthere is provided a system for tracking a position of an intra-bodycatheter, comprising: an output interface for communicating with adisplay; an electrode interface for communicating with a plurality ofphysical electrodes on a distal end portion of a physical catheterdesigned for intra-body navigation; a program store storing code; and aprocessor coupled to the output interface, the electrode interface, andthe program store for implementing the stored code, the code comprising:code to receive measurements of a plurality of electrical fields appliedwithin the body portion, measured by the plurality of physicalelectrodes; code to calculate and physically track coordinates of theposition of the distal end of the physical catheter within the physicalbody portion of the patient; code to register the physically trackedcoordinates with simulation coordinates generated according to asimulation of a simulated catheter within a simulation of the body ofthe patient, to identify differences between physically tracked locationcoordinates and the simulation coordinates; code to correct thephysically tracked location coordinates obtained according to thesimulation coordinates; and code to transmit the corrected physicallytracked location coordinates to the output interface.

Optionally, the system further comprises an imaging interface forcommunicating with an imaging modality that acquires a dataset ofanatomical imaging data of a patient; wherein the processor is furthercoupled to the imaging interface; code to receive the dataset, andassociate at least one dielectric parameter value corresponding todifferent tissues of the anatomical imaging data of the dataset, whereinthe at least one dielectric parameter value represents an initialestimated value; and code to generate the simulation that trackscoordinates of a position of the simulated catheter within the datasetrepresenting the body portion according to simulated application of aplurality of electrical fields within the body portion and measurementsof the electrical field performed by a plurality of electrodes at adistal portion of the catheter. Optionally, the dataset includes threedimensional (3D) anatomical imaging data acquired by at least one of aCT and an MRI. Optionally, the corrected physically tracked locationcoordinates are displayed within a presentation of the dataset.

Optionally, the system further comprises a connector having a first portfor connecting to the physical catheter, a second port for connecting toa control unit associated with the physical catheter, and a third portfor connecting to the electrode interface, the connector includingcircuitry to intercept signal transmission between the physical catheterand the control unit and transmit the intercepted signals to theelectrode interface without interfering with the signal transmissionbetween the physical catheter and the control unit.

According to an aspect of some embodiments of the present inventionthere is provided a catheter for insertion into a pericardial space andmeasuring a dielectric property of a portion of a myocardium within thepericardial space, comprising: a plurality of sensors spaced apart anddisposed at a distal end portion of a catheter, the plurality of sensorsarranged to contact a visceral pericardium in contact with a myocardiumof a heart, the plurality of sensors arranged to measure at least onedielectric property of a portion of a myocardium; and an isolationelement disposed at a distal end portion of a catheter, the isolationelement arranged to physically isolate a region of a parietalpericardium from contact with a region of the visceral pericardiumbetween the plurality of sensors in contact with the visceralpericardium; wherein the distal end portion of the catheter is adaptedfor expansion within the pericardial space, from a first contractedstated wherein the distal end portion of the catheter is sized forinsertion a pericardial space, to a second expanded state, whereinduring the expanded state the plurality of sensors contact the visceralpericardium and the isolation element physically isolates the regionbetween the sensors from the parietal pericardium.

Optionally, the isolation element is arranged to apply a contact forcebetween the plurality of sensors and the visceral pericardium.

Optionally, the plurality of sensors are in communication with aninterface of a unit, the unit comprising: a sensor interface forcommunicating with the plurality of sensors; a program store storingcode; and a processor coupled to the sensor interface, and the programstore for implementing the stored code, the code comprising: code toreceive signals from the plurality of sensors and calculate an impedanceof the myocardium.

Optionally, the isolation element is a strut arranged in a U shape inthe expanded state, wherein the plurality of sensors are disposed on thedistal arms of the U, and the arc of the U is arranged to urge theparietal pericardium away from the visceral pericardium to form theisolated region.

Optionally, the isolation element is arranged to physically isolate aregion of the parietal pericardium from contact with a region of thevisceral pericardium in near proximity around the plurality of sensorsin contact with the visceral pericardium. Optionally, the sensors aredesigned to measure a real and imaginary impedance componentsubstantially concomitantly at a first frequency of about 40 kHz and ata second frequency of about 1 MHz.

According to an aspect of some embodiments of the present inventionthere is provided a computerized method for tracking a position of anintra-body catheter, comprising: receiving location coordinates of acatheter within a body of a patient, the location coordinates measuredbased on applied electric fields; and correcting the locationcoordinates according to a simulation of the catheter within the bodybased on a dielectric map including acquired anatomical imaging data ofthe patient and at least one dielectric parameter value corresponding toone or more different tissues identified within the anatomical imagingdata.

According to an aspect of some embodiments of the present inventionthere is provided a system for tracking a position of an intra-bodycatheter, comprising: an output interface for communication with adisplay; an input interface for communication with a navigation system;a program store storing code; and a processor coupled to the inputinterface, the output interface, and the program store for implementingthe stored code, the code comprising: code to receive, via the inputinterface, location coordinates of a catheter within a body of apatient, the location coordinates measured based on applied electricfields; code to correct the location coordinates according to asimulation of the catheter within the body based on a dielectric mapincluding acquired anatomical imaging data of the patient and at leastone dielectric parameter value corresponding to one or more differenttissues identified within the anatomical imaging data; and code toprovide the corrected location coordinates to the output interface forpresentation on the display.

According to an aspect of some embodiments of the present inventionthere is provided a method for estimating contact force between anintra-body catheter and a tissue of a body of a patient, comprising:receiving, at least one impedance measurement of a tissue of a patientin contact with an intra-body catheter, the at least one impedancemeasurement based on a signal transmitted between at least one electrodeon the intra-body catheter in contact with the tissue and at least oneother electrode; analyzing the at least one impedance measurementaccording to a trained machine learning method that correlates the atleast one impedance measurement with an estimated applied force, whereinthe trained machine learning method is based on a fitted correlationbetween multiple impedance values measured at multiple locations of asample tissue similar to the tissue of the body of the patient; andproviding the estimated applied force for presentation to a user.

Optionally, the analyzing comprises correlating the at least oneimpedance measurement with an applied contact force category.Optionally, the applied contact force category is selected from thegroup consisting of: suboptimal contact force, optimal contact force,and excessive contact force.

According to an aspect of some embodiments of the present inventionthere is provided a method for estimating at least one dimension of anablated tissue lesion from at least one impedance measurement,comprising: receiving, at least one impedance measurement of a tissue ofa patient in contact with an intra-body catheter, the at least oneimpedance measurement based on a signal transmitted between at least oneelectrode on the intra-body catheter in contact with the tissue and atleast one other electrode; analyzing the at least one impedancemeasurement according to a trained machine learning method thatcorrelates the at least one impedance measurement with at least oneestimated dimension of the ablated tissue, wherein the trained machinelearning method is based on a fitted correlation between multipledimensions measured at multiple locations of a sample tissue similar tothe tissue of the body of the patient; and providing the estimated atleast one dimension for presentation to a user.

Optionally, the at least one impedance measurement of the tissue isreceived at least one of: before an ablation of the tissue and after theablation of the tissue.

Optionally, the at least one dimension is selected from the groupconsisting of: depth, surface diameter, and volume.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

Implementation of the method and/or system of embodiments of theinvention can involve performing or completing selected tasks manually,automatically, or a combination thereof. Moreover, according to actualinstrumentation and equipment of embodiments of the method and/or systemof the invention, several selected tasks could be implemented byhardware, by software or by firmware or by a combination thereof usingan operating system.

For example, hardware for performing selected tasks according toembodiments of the invention could be implemented as a chip or acircuit. As software, selected tasks according to embodiments of theinvention could be implemented as a plurality of software instructionsbeing executed by a computer using any suitable operating system. In anexemplary embodiment of the invention, one or more tasks according toexemplary embodiments of method and/or system as described herein areperformed by a data processor, such as a computing platform forexecuting a plurality of instructions.

Optionally, the data processor includes a volatile memory for storinginstructions and/or data and/or a non-volatile storage, for example, amagnetic hard-disk and/or removable media, for storing instructionsand/or data. Optionally, a network connection is provided as well. Adisplay and/or a user input device such as a keyboard or mouse areoptionally provided as well.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and for purposes of illustrativediscussion of embodiments of the invention. In this regard, thedescription taken with the drawings makes apparent to those skilled inthe art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a flowchart of a method for tracking the position of anintra-body catheter, in accordance with some embodiments of the presentinvention;

FIG. 2 is a block diagram of components of a system for tracking theposition of an intra-body catheter, in accordance with some embodimentsof the present invention;

FIG. 3 is a flowchart of a method for selecting one or more parametersfor tracking the position of an intra-body catheter, in accordance withsome embodiments of the present invention;

FIG. 4 is a flowchart of a method of iteratively updating a simulationof the position of an intra-body catheter, in accordance with someembodiments of the present invention;

FIG. 5 is a flowchart of a method for estimation volume and/or depth ofan ablated lesion, and/or for estimating a contact force applied by theintra-body catheter to a tissue, in accordance with some embodiments ofthe present invention;

FIG. 6 is a flowchart of another method for estimating quality ofcontact between the intra-body catheter and a tissue based on tracking atrajectory of motion of the contacting catheter portion, in accordancewith some embodiments of the present invention;

FIG. 7 is a flowchart of a method for identifying regions of fibrotictissue, in accordance with some embodiments of the present invention;

FIG. 8A is a schematic of a catheter for measuring one or moredielectric properties of the myocardium from within the pericardialspace which may be used with the method of FIG. 1 and/or system of FIG.2, in accordance with some embodiments of the present invention;

FIGS. 8B-C are some designs of the catheter of FIG. 8A, in accordancewith some embodiments of the present invention;

FIG. 9 is a schematic diagram of a connector for connecting a catheterto the system of FIG. 2, in accordance with some embodiments of thepresent invention;

FIG. 10 is a graph of an example of multiple impedance measurementsobtained by an electrode on a catheter, and an associated measuredforce, useful for generating a model for real-time force estimationbased on real-time impedance measurements, in accordance with someembodiments of the present invention;

FIGS. 11A-B are example graphs depicting a correlation between anestimation of the depth of an ablated tissue lesion based on impedancemeasurements, and a measured depth, in accordance with some embodimentsof the present invention;

FIG. 12 is flowchart of a method for generating the thermal component ofa generated simulation, in accordance with some embodiments of thepresent invention;

FIG. 13A is a graph depicting the calculated PLD pattern created by anelectrode (e.g., RF ablation electrode(s)) in a tissue, in accordancewith some embodiments of the present invention; and

FIG. 13B is a graph depicting the calculated temperature pattern (indegrees Celsius) created by an electrode (e.g., RF ablationelectrode(s)) in a tissue, in accordance with some embodiments of thepresent invention.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to systemsand methods for tracking intrabody catheters and, more particularly, butnot exclusively, to systems and methods for non-fluoroscopic tracking ofintrabody catheters.

One form of catheter ablation known as RF ablation relies heating causedby the interaction between a high-frequency alternating current (e.g.,350-500 kilohertz ((kHz)) introduced to a treatment region, anddielectric properties of material (e.g., tissue) in the treatmentregion. One variable affecting the heating is the frequency-dependentrelative permittivity κ of the tissue being treated. The (unitless)relative permittivity of a material (herein, κ or dielectric constant)is a measure of how the material acts to reduce an electrical fieldimposed across it (storing and/or dissipating its energy). Relativepermittivity is commonly expressed as

${\kappa = {{ɛ_{r}(\omega)} = \frac{ɛ(\omega)}{ɛ_{0}}}},$where ω=2πf, and f is the frequency (of an imposed signal, for example,voltage). In general, ε_(r)(ω) is complex valued; that is:ε_(r)(ω)=ε′_(r)(ω)+iε″_(r)(ω).

The real part ε′_(r)(ω) is a measure of energy stored in the material(at a given electrical field frequency and/or voltage and/or amplitude),while the imaginary part ε^(n) _(r)(ω) is a measure of energydissipated. It is this dissipated energy that is converted, for example,into heat for ablation. Loss in turn is optionally expressed as a sum ofdielectric loss ε^(n) _(rd) and conductivity σ as

${ɛ_{r}^{''}(\omega)} = {ɛ_{rd}^{''} + {\frac{\sigma}{\omega \cdot ɛ_{0}}.}}$

Any one of the above parameters: namely κ, ε, ε^(k) _(r), σ, and/orε^(n) _(rd), may be referred to herein as a dielectric parameter(sometimes referred to herein as electric parameter). The termdielectric parameter encompasses also parameters that are directlyderivable from the above-mentioned parameters, for example, losstangent, expressed as

${{\tan\;\sigma} = \frac{ɛ_{r}^{''}}{ɛ_{r}^{\prime}}},$complex refractive index, expressed as n=√{square root over (ε_(r))},and impedance, expressed

${{as}\mspace{14mu}{Z(\omega)}} = {\sqrt{\frac{i\;\omega}{\sigma + {i\;\omega\; ɛ_{r}}}}\mspace{14mu}{\left( {{{with}\mspace{14mu} i} = \sqrt{- 1}} \right).}}$

Herein, a value of a dielectric parameter of a material may be referredto as a dielectric property of the material. For example, having arelative permittivity of about 100000 is a dielectric property of a0.01M KCl solution in water at a frequency of 1 kHz, at about roomtemperature (20°, for example). Optionally, a dielectric property morespecifically comprises a measured value of a dielectric parameter.Measured values of dielectric parameters are optionally providedrelative to the characteristics (bias and/or jitter, for example) of aparticular measurement circuit or system. Values provided bymeasurements should be understood to comprise dielectric properties,even if influenced by one or more sources of experimental error. Theformulation “value of a dielectric parameter” is optionally used, forexample, when a dielectric parameter is not necessarily associated witha definite material (e.g., it is a parameter that takes on a valuewithin a data structure).

Dielectric properties as a function of frequency have been compiled formany tissues, for example, C. Gabriel and S. Gabriel: Compilation of theDielectric Properties of Body Tissues at RF and Microwave Frequencies(web pages presently maintained at//niremf.ifac.cnr.it/docs/DIELECTRIC/home.html).

An aspect of some embodiments of the present invention relates tosystems and/or methods (e.g., code) for tracking the position of adistal end portion of an intra-body catheter (e.g., tracking theposition of one or more electrodes and/or sensors located on catheter,e.g., the distal end thereof), by correcting a position (e.g.,coordinates) of the distal end portion measured according to one or moreelectrical and/or dielectric and/or thermal parameters (e.g., field,current, voltage, and/or impedance), by correlation with a simulation.The simulation may include simulated positions of a simulated intra-bodycatheter within an acquired anatomical imaging dataset of the patient,the dataset associated with estimated dielectric parameter values and/orwith estimated thermal parameter values. The corrected position of thedistal end may be displayed, for example, on a screen within theacquired anatomical image of the patient. The systems and/or methods mayimprove the accuracy of the position measured according to theelectrical parameters and/or the thermal parameters with the correctionaccording to the simulation. In this manner, the relatively higheraccuracy may allow to perform treatment procedures that require a higherdegree of accuracy in positioning of the distal end of the catheter, forexample, neuromodulation and/or ablation; e.g., neuromodulation and/orablation of ganglionic plexi (GP) or other nervous tissues (e.g., neuralfibers, neural synapses, neural sub-systems, and/or organ specificnervous tissue) in the wall of the heart and/or other organs and/ortissues (e.g., carotid body, aortic arch, pulmonary, renal, splenic,hepatic, inferior mesenteric, superior mesenteric, muscular and/or,penile nervous tissue).

Optionally, the simulation is iteratively updated according to one ormore parameters measured in real-time, for example, electricalparameters and/or thermal parameters of tissues by intra-body sensors,optionally dielectric parameters, such as impedance of the myocardium ofthe heart (or other target-related tissue), and/or conductivity of theblood, and/or thermal parameters such as thermal conductivity and/orheat capacity. The measured values may be fed back into the simulation,to update the estimated electrical values and/or thermal values with themeasured parameters values. The simulation may be re-generated togenerate an updated set of simulated positions for correcting themeasured physical location of the distal end of the catheter.Optionally, the measuring and updating of the simulation are iterated,to improve the accuracy of the corrected distal end position. Theiteration may be performed to reach a target accuracy, such as anaccuracy fine enough for performing the treatment procedure.

Optionally, the iterations of updating the simulation are performed onselected sub-volumes within the dataset, optionally including the targettissue and the distal end of the catheter. As the catheter is navigatedtowards the target tissue, the selected sub-volume may decrease. Thedecreased simulated volume may achieve relatively higher accuracy in theposition of the distal end of the catheter. For example, as theprocedure is performed, and the catheter is navigated from a vascularaccess point toward a target region inside a heart chamber for ablation,the simulation is updated, and the accuracy of the position of thecatheter distal end increases, until the highest accuracy is reachedwhen the distal end is in close proximity to the target tissue.

Optionally, the simulation tracks the position of the simulated distalend of the catheter during a simulation of the prospective procedure,for example, intra-cardiac ablation. The simulation may estimate theposition of the simulated distal end according to simulated measurementsperformed by simulated electrodes at the simulated distal end ofsimulated electric parameters generated by multiple extra-bodypositioned electrodes (e.g., on the skin of the simulated patient).

Optionally, one or more parameters of the simulation are adjusted in apre-planning phase, which may be performed off-line, before the patientundergoes the procedure. The error in accuracy (and/or absoluteaccuracy) of calculating the location of the distal end may be estimatedfor each adjusted parameter. The parameter that is associated with therelatively lowest error in accuracy and/or relatively highest accuracymay be selected. The pre-planning phase may select the adjustedparameters before the patient undergoes the procedure, for use duringthe procedure. The parameters selected in the pre-planning phase may berelated to the extra-body electrodes, for example, to select theextra-body electrodes and/or position of the extra-body electrodes inadvance, for use during the procedure. The simulation may select theparameters to achieve the lowest error and/or highest accuracy. Thesimulated parameters may alter the measurements of the electric fieldmeasured by the sensors at the distal end of the catheter and/or alterdielectric and/or thermal measurements of tissues, by altering theelectric and/or thermal parameters of tissues. The alternation of theelectric field measurements by the parameter(s) may introduce error intodetermination of the coordinates representing the location of thecatheter using the electric field. The simulation of the parametershelps determine the actual location of the catheter, by determining therequired correction of the measurements according to the simulation. Theparameters may relate to one or more additional catheters that are usedin the procedure being simulated. The parameters may be related to thecross-talk caused by the one or more additional catheters with theoriginal catheter. The simulation may select one or both of thecatheters (e.g., from commercially available catheters) to reducecross-talk, which may reduce the error and/or improve accuracy ofdetecting the position. Alternatively or additionally, the parametersmay be related to simulating the effect of drugs, for example, theestimated effect on ionic concentration in the body resulting from thedrugs, which affects the electrical parameters. Alternatively oradditionally, the parameters may be related to simulating the effects ofdisease, for example, reduced elasticity in the vasculature due to anexisting medical condition, or the presence of tumors in body organs.Alternatively or additionally, the parameters may be related tosimulating the effects of the treatment being planned, to help determinewhether the treatment will help the patient or not. Alternatively oradditionally, the parameters may be related to simulating the effect ofmechanical force, for example, the effect of puncturing the heart septumfor access from one atrium to another. Alternatively or additionally,the parameters may be related to simulating the effects of deliveringthermal intervention, such as hyperthermia, or freezing, for example, bysimulating the temperature effects on the tissue and/or resultingeffects on electrical values. Alternatively or additionally, theparameters may be related to simulating the effects of transmittingsignal(s) into the body from outside the body, for example, the effectsof the signal on the electrical and/or thermal parameters of thetissues. Alternatively or additionally, the parameters may be related tosimulating the effects of transmitting signal(s) to the outside of thebody from inside the body, for example, the effects of the signal on theelectrical and/or thermal parameters of the tissues. Alternatively oradditionally, the simulation is updated in real-time, based on real-timemeasurements (e.g., impedance measurements) obtained during theprocedure, as described herein. The parameters may improve accuracy ofthe generated simulation, by considering one or more real-timeparameters that may occur during the procedure, and the way in whichthose parameters affect the electric and/or thermal properties of thetissues.

Optionally, the simulation includes a simulation of ablation of targettissue within the acquired dataset correlated with one or more estimatedelectric and/or thermal parameters of the ablated tissue (and/or nearbytissue). The simulation may include the progression of the ablationlesion over time, correlated with contact force, tissue dielectricparameters (e.g., impedance), tissue thermal parameters, and/or othervalues. The simulated ablation may be used for lesion assessment basedon real-time dielectric measurements (e.g., impedance) and/or thermalmeasurements of tissues. The simulation may include a correlationbetween the one or more estimated electric and/or thermal parameters andprogress of the ablation, such as the size, volume, and/or depth of theablated tissue. The simulation may include a correlation of the qualityof contact between the distal end of the catheter and the tissue (i.e.,the target tissue and/or nearby tissue), with the electrical and/orthermal parameters of the tissue. In this manner, real-time measurementof the dielectric and/or thermal parameters of the tissues (e.g.,impedance measures of the tissues using electrodes of the distal end)may be correlated with the quality of contact (which may be presented tothe operator). The quality of contact may be estimated based on machinelearning methods applied to pre-acquired data (e.g., empirical dataand/or calculated values). Alternatively or additionally, the real-timemeasurements of the dielectric and/or thermal parameters may becorrelated with the simulated ablation, to provide an estimatedassessment of the lesion progress. The lesion assessment may beestimated based on machine learning methods applied to pre-acquired data(e.g., empirical data and/or calculated values).

The operator, in response to the presentation, may adjust the contact(e.g., higher force or less force) to try and obtain optimal contact.The quality of contact may be correlated with the volume and/or depth ofthe ablation lesion, for example, the volume and/or depth of the lesionmay be estimated for good quality contact. In this manner, the absolutecontact force to achieve the ablation (e.g., in grams) does not need tonecessarily be measured and/or estimated, instead, being estimatedaccording to the measured electrical and/or thermal parameter. As such,the contact force may be classified, for example, into three categories:good contact (e.g., for ablation), suboptimal contact (e.g., more forceneeded), and excessive contact (e.g., reduction in force needed), whichmay be more clinically relevant to the physician than an absolute valueof the measured contact force.

Alternatively or additionally, a trajectory of the motion of the distalend (e.g., due to pulsatile motion related to heart contractions) isanalyzed to estimate the quality of the contact force. The trajectory ofthe motion of the distal end may be correlated with a simulatedtrajectory of the motion of the tissue in contact with the distal end,which moves due to the heart contractions. The trajectory of the motionmay be correlated with other data representing heart contractions, forexample, an electrocardiogram (ECG). The quality of contact may beestimated based on the correlation, for example, a high correlationrepresents good quality contact, and a poor correlation represents poorquality contact.

Optionally, multiple real-time measurements of electric and/or thermalparameters (e.g., impedance measurements by electrodes on the distal endof the catheter, and/or thermal conductivity, and/or heat capacity) oftissues, each performed at a different location of the distal end, areanalyzed to identify electrical and/or thermal tissue signature(s)indicative of a region of fibrosis, for example, a scar due to aprevious surgery, fibrotic tissue due to a previous ablation, and/ornaturally occurring fibrotic tissue. Optionally, the phase value of themeasured impedance may be used to analyze and/or identify the electricaltissue signature(s). The identified fibrotic regions may be mapped tothe dataset, such as for presentation to the user. In this manner, thefibrotic regions may be visually identified by the operator, and avoidedduring the ablation procedure. The identified fibrotic regions map beinputted into the simulation in real-time, to update the simulation.

An aspect of some embodiments of the present invention relates tosystems and methods for medical treatment and/or diagnosis using firstand second information sources.

The first information source may be used for pre planning phase (e.g.,for planning a treatment procedure). The first information source mayinclude electro-magnetic (EM) simulation tool and/or thermal simulationtool. The first information source may receive a dataset of a bodyportion of a patient including anatomical imaging data of the patient(optionally 3D data), for example, acquired from imaging modality.Optionally, the provided imaging dataset includes associated dielectricand/or thermal parameter values. Optionally, the imaging data wasacquired before the treatment procedure.

The second information source may be used in the treatment phase (e.g.,based on real-time data). For example, information may be obtainedduring the treatment procedure. Optionally, the second informationsource may receive real-time measurement, e.g., real-time measurement ofone or more dielectric and/or thermal parameter(s) of one or moreintra-body organs being treated (e.g., a dielectric and/or thermalmap(s)).

In some embodiments, information from the second information source isfed to the first information source (for example: real-time measurementof one or more dielectric and/or thermal parameter(s)). Such informationfrom the second information source may modify the first informationsource output (e.g., the simulation may be updated to obtain updatedsimulation). Optionally, the updated simulation is more accurate than aninitial simulation (e.g., simulation calculated in the pre-planningphase).

Optionally, information from the first information source may altersecond information source output. For example, updated information fromthe first information source may be fed back to the second informationsource, e.g., may be used to change the thresholds used for example tojudge the appropriateness of the treatment based on the real timemeasurements.

In yet another example, after a successful ablation of a point in anablation line, the properties of the heart change and thus thedielectric parameter guiding the treatment in real time are differentthan the ones generated from first information source prior to theprocedure, such changes in dielectric parameters may be inputted to thefirst information source for updating the simulation.

An aspect of some embodiments of the present invention relates to acatheter for insertion into narrow and/or small tissue region, forexample, a collapsed region and/or a potential body space, for example,a pericardial space of a heart of a patient, a pleural space of a lungof a patient, for measuring one or more dielectric and/or thermalproperties of a portion of a myocardium within the pericardial space,optionally impedance and/or conductance of the pericardium. The distalend portion of the catheter may include multiple sensors arranged tocontact the visceral pericardium to measure the dielectric propertyand/or the thermal property. The distal end portion of the catheter mayinclude an isolation element arranged to physically isolate a region ofthe parietal pericardium from contact with a region of the visceralpericardium between the sensors in contact with the visceralpericardium, optionally including an isolated region around the sensors.In this manner, as the sensors do not come in contact with the parietalperitoneum, the sensors measure the dielectric and/or thermal propertyof the myocardium while preventing or reducing errors in measurement dueto interference from other nearby tissues in contact with the parietalpericardium.

An aspect of some embodiments of the present invention relates to amethod for estimating contact force between an intra-body catheter and atissue of a body of a patient, for example, to help control an ablationprocedure. The method may be implemented by code stored in a programstore, implementable by a processor of a computing unit (e.g., asdescribed herein). The method may apply a trained machine learningmethod (e.g., statistical classifier, a fitted parametric model, one ormore functions, a look-up table, support vector machine with optionalradial basis functions) to correlate one or more impedance measurements(optionally measured in real-time during a procedure) with an estimatedapplied contact force. The impedance measurements may be performed by anelectrode on the catheter contacting the tissue, to estimate the contactforce between the catheter and the tissue. The impedance measurementsmay be performed by a plurality of electrodes. Inventors discovered thatthe machine learning method, trained using a set of multiple measuredimpedance values at different locations on similar tissue (i.e., fromother patients), may correlate the real-time impedance measurement tothe estimated force with sufficient accuracy to allow the operatorperforming the procedure to control the force application to help arriveat a desired treatment result (e.g. ablation). Inventors discovered,that even when the variability of the training set is large, thecorrelation between the real-time impedance measurement and appliedforce may be clinically significant. Optionally, the correlation isperformed to an applied contact force category, which may be clinicallysignificant (i.e., helps guide the operator to perform the desiredablation).

Optionally, the applied contact force categories include: suboptimalcontact force, optimal contact force, and excessive contact force. Inthis manner, the operator may not necessarily be provided with theabsolute force, instead, being provided with a relative measure orcategory that is clinically relevant to the procedure. The relativecategory may be more easily acted upon by the operator, for example, byincreasing the force, reducing the force, or maintaining the force.

Alternatively or additionally, another trained machine learning methodis applied to correlate the one or more impedance measurements with anestimated dimension or spatial data of the ablated tissue lesion,optionally one or more of: depth, surface diameter, and volume.Optionally, the real-time impedance measurements are obtained before theablation procedure. Alternatively or additionally, the real-timeimpedance measurements are obtained after the ablation procedure.

The systems and/or methods described herein may provide a technicalsolution to the technical problem of improving navigation of a catheterwithin the body of a patient, and/or improving control of a catheterbased ablation procedures. The location of the catheter within the bodyof the patient and/or the procedure being performed cannot be directlyvisualized. Use of X-ray based image guidance (e.g., fluoroscopy)delivers energy to the body of the patient, and is to be reduced oreliminated. Use of other navigation methods (e.g., relative toexternally applied electromagnetic fields) may not be accurate enough toperform fine procedures, such as ablation.

In some embodiments, the systems and/or methods described herein may tiemathematical operations (e.g., performing calculations to generate thesimulation) to the ability of a processor to execute code instructions,and to one or more sensors that measure actual data in real-time (e.g.,from within the body of the patient) that is used by the processor toupdated and improve the generated simulation.

In some embodiments, the systems and/or methods described herein mayimprove performance of computer(s) (e.g., client terminal, server),and/or networks, and/or medical imaging equipment and/or medicaltreatment equipment (e.g., RF catheters). For example, the improvementin accuracy obtained by updating the generated simulation usingreal-time measured electrical and/or thermal values (as describedherein), may reduce the amount of medical imaging required (e.g., interms of radiation dose, processing of the images, and memory to storethe images) by improving the navigation and/or guidance of the catheter.

In some embodiments, the systems and/or methods described herein maycreate new data in the form of an updated simulation. The data of theupdated simulation may be organized in a specific manner, to allowiterative updates of portions of the data according to real-timemeasurements.

In some embodiments, the systems and/or methods described herein mayprovide a unique, particular, and advanced technique of using real-timemeasurements to update a generated simulation, which is used inreal-time to guide a catheter, for example, to navigate a catheterand/or perform a medical treatment on tissue.

Accordingly, the systems and/or methods described herein are necessarilyrooted in computer technology to overcome an actual technical problemarising in guidance and/or control of instruments (e.g., catheters)within the body of a patient, for example, to perform ablation basedtreatment and/or navigation of the instrument.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not necessarily limited in itsapplication to the details of construction and the arrangement of thecomponents and/or methods set forth in the following description and/orillustrated in the drawings and/or the Examples. The invention iscapable of other embodiments or of being practiced or carried out invarious ways.

As used herein, the term distal end is sometimes interchanged with theterm catheter, for example, for tracking the position thereof. The termdistal end is not meant to be necessarily limiting, serving as anexample of the portion of the catheter being tracked, such as accordingto the location of the sensors and/or electrodes on the catheter. Assuch, other locations of the catheter may be tracked, and may sometimesbe interchanged for the term distal end, for example, distal endportion, region away from the distal end, catheter portion, and/or otherregions of the catheter.

As used herein the term ablation, for example, ablation treatment maymean application of energy by an instrument (e.g., catheter) to tissue,for example, RF, ultrasound, cryo energy (to cool the tissue), andthermal energy (to heat the tissue). The ablation is applied to attemptto reach a desired therapeutic effect, which may or may not includekilling of cells.

Referring now to the drawings, FIG. 1 is a flowchart of a method fortracking the position of an intra-body catheter, in accordance with someembodiments of the present invention. The method receives a datasetrepresenting an anatomical image (e.g., 3D CT images) of the patient,and based on dielectric properties of tissue types (e.g., impedanceand/or conductivity) and/or thermal properties (e.g., thermalconductivity, heat capacity, and metabolic heat generation) identifiedwithin the anatomical image, creates a dielectric map and/or a thermalmap (i.e., dataset) for the patient. The dielectric and/or thermal mapis used as a basis for a generating a simulation of a simulated catheterduring a simulated procedure, according to simulated positions ofsimulated extra-body electrodes. The output of the simulation is used tocorrect real-time readings of position data (e.g., of the distal end ofa catheter) measured based on electric and/or thermal parameters (e.g.,voltage, electric field, impedance, current).

The thermal parameters may include general thermal properties which maydefine living tissue and inanimate matter, for example, thermalconductivity and/or het capacity, and/or thermal properties specific tobiological tissues, for example, metabolic heat generation, absorptionrate, and blood perfusion rate. The thermal properties may be used asinputs into a bio heat formulation of a heat equation to estimatetemperature evolution in the region of interest as a function of timeand/or space.

The electric and/or dielectric parameter values may be associated withthe thermal parameter values. The electric and/or dielectric propertiesmay be temperature and/or frequency dependent. Estimation of thedielectric parameter values may be improved by simulating the thermalparameters, and/or measuring and/or calculating the thermal parametersin real time. As used herein, the term electric may mean electric and/orthermal. The term dielectric may mean dielectric and/or thermal.

The method may improve the accuracy of the original received positiondata. Reference is also made to FIG. 2, which is a block diagram ofcomponents of a system for tracking the position of an intra-bodycatheter, in accordance with some embodiments of the present invention.The system of FIG. 2 may allow for an operator to perform intra-bodyprocedures that require relatively higher accuracy than the accuracyprovided by existing electric parameter based systems, for example,radiofrequency ablation, and/ injection (e.g., chemical) based ablation,e.g., of GPs.

The method of FIG. 1 and/or system of FIG. 2 may be used to iterativelycorrect the location data and/or improve the accuracy of the locationdata by integration of real-time measurements that are used to updatethe simulation, for example, measurements of the impedance and/orconductance of the myocardium and/or blood and/or other tissues. Thesystem of FIG. 2 may execute the method of FIG. 1.

It is noted that the method of FIG. 1 and/or the system of FIG. 2 maycorrect the location of the distal end of the catheter by separately andsubstantially simultaneously tracking the position of sensors,electrodes and/or other conducting ports on the distal end of thecatheter. The distance between sensors on the distal end of the cathetermay be used for calibration, as described herein. The location of thecatheter may be derived based on the locations of the multiple sensorson the catheter's distal end.

As used herein, the terms sensor and electrode are sometimesinterchangeable, for example, where referring to an element thatperforms measurements of one or more electrical properties (e.g.,dielectric properties, conductance, impedance, voltage, current, and/orelectrical field strength). For example, the electrodes may function asthe sensors, such as by transmitting from one electrode to a secondelectrode, where the second electrode functions as a sensor. Impedancemay be measured between respective electrode pairs, and/or between adesignated electrode and a reference electrode (which may be locatedoutside the body and/or within the body, such as on the catheter).

The method of FIG. 1 and/or system of FIG. 2 may provide additionalfeatures, for example, selection of the electric and/or thermalparameters (and/or elements that generate the electric and/or thermalparameters), estimation of contact force applied by the distal end ofthe catheter to the tissue wall, estimation of the lesion formation(e.g., size, volume and/or depth), estimation of tissue temperature,and/or mapping of fibrotic regions.

System 200 may include a program store 206 storing code (as describedherein) and a processor 204 coupled to program store 206 forimplementing the stored code. Optionally, more than one processor may beused. It is noted that program store 206 may be located locally and/orremotely (e.g., at a remote server and/or computing cloud), with codeoptionally downloaded from the remote location to the local location forlocal execution (or code may be entirely or partially executedremotely).

System 200 may include an imaging interface 210 for communicating withone or more anatomical imaging modalities 211 that acquire a dataset ofimaging data of a patient, for example, anatomical imaging data, e.g., acomputer tomography (CT) machine, an ultrasound machine (US), a nuclearmagnetic resonance (NM) machine, a single photon emission computedtomography (SPECT) machine, a magnetic resonance imaging (MRI) machine,and/or other structural and/or functional anatomical imaging modalitymachines. Optionally, imaging modality 211 acquires three dimensional(3D) data and/or 2D data. It is noted that the anatomical images may bederived and/or acquired from functional images, for example, fromfunctional images from an NM machine.

System 200 may include an output interface 230 for communicating with adisplay 232, for example, a screen or a touch screen. Optionally, thecorrected physically tracked location coordinates are displayed within apresentation of the dataset, for example, the 3D acquired anatomicalimages are displayed on display 232, with a simulation of the locationof the distal end of the catheter within the displayed image based onthe corrected location.

System 200 may include an electrode interface 212 for communicating witha plurality of physical electrodes 214 and/or sensors (e.g., theelectrodes may serve as the sensors) located on a distal end portion ofa physical catheter 216 designed for intra-body navigation, for example,an electrophysiology (EP) ablation catheter, and/or other ablationcatheter (e.g., chemical ablation or injection catheter). Alternativelyor additionally, system 200 includes a navigation interface 234 forcommunicating with a catheter navigation system 236, optionally anon-fluoroscopic navigation system, optionally, an impedance measurementbased system.

The intra-body navigation may be performed based on extra-bodyelectrodes that receive and/or transmit current (e.g., alternatingcurrent) in different frequencies and/or different times betweenco-planar directions. Analysis of the electrical and/or thermalparameters obtained from the sensors of the catheter, separated into thedifferent channels may be used to estimate the location of each sensorrelative to each extra-body electrode. A calibration of the distancesbetween the sensors (e.g., based on manufacturing specifications of thecatheter, and/or measurements such as using fluoroscopy or othermethods) may be performed.

Optionally, system 200 includes a sensor interface 226 for communicatingwith one or more sensors 228, which may be in the body or external tothe body, for example, for measuring electrical and/or thermalparameters, for example, impedance and/or conductivity and/or thermalconductivity and/or heat capacity and/or metabolic heat generation ofthe blood, the myocardium, and/or other tissues, for example, thecatheter described herein with reference to FIGS. 8A-8C, and/or othermethods described herein.

Optionally, system 200 may include a data interface 218, forcommunicating with a data server 222, directly or over a network 220, toacquire estimated dielectric and/or thermal tissue values forassociation with the acquired imaging dataset. Alternatively, theestimated dielectric and/or thermal values are stored locally, forexample, on data repository 208.

Optionally, a user interface 224 is in communication with data interface218, for example, a touch screen, a mouse, a keyboard, and/or amicrophone with voice recognition software.

Optionally, system 200 (e.g., computing unit 202) includes a connector240 connecting between catheter 216 (e.g., RF ablation catheter,injection catheter) and a connector interface 242 (and/or electrodeinterface 212). Connector 240 may be used to adding additional featuresto existing catheters, such as off the shelf catheters, for example, RFablation catheters, at least by acting as an input of signalscommunicated by the catheter for processing by system 200. The signalscommunicated by the catheter are intercepted by circuitry withinconnector 240 and transmitted to interface 242 and/or 212, withoutinterfering with the signal transmission. The intercepted signals may beanalyzed by system 200, for example, to perform real-time tissuemeasurements (e.g., contact force, pressure, ablated volume and/ordepth, temperature, and/or fibrosis mapping, as described herein), toperform localization of the catheter (e.g., as described herein), toidentify the type of the catheter, and/or to identify the presence ofconnector 240.

Connector 240 may be implemented, for example, as shown with referenceto FIG. 9, which is a schematic diagram of a connector 902(corresponding to connector 240) for establishing communication betweensystem 200 and a catheter, in accordance with some embodiments of thepresent invention. According to some embodiments, connector 902 is anelement having 3 ports 904, 906, and 908 (e.g., a T shape, a Y shape,optionally having a round cross-section). Connector 902 may be designedto fit existing connectors of catheters that connect to control devices(e.g., an ablation control unit), for example, an 18 pin male to femaleconnector. A first port 904 connects to the catheter end, a second port908 connects to the control unit, and a third port 906 connects toconnector interface 242 (or electrode interface 212) of unit 202.

Extension cables may be used to connect each respective port. Connector902 may directly couple (e.g., plug) between the proximal end of thecatheter and the respective extension cable. It is noted that the portsmay be arranged in a different configuration.

Connector 902 may be designed to monitor signals between the coupledcatheter and control unit, without interfering with signal transmissionand/or otherwise changing the transmitted signals. Optionally, connector902 includes pre-amplifiers for intercepted analog signals beinginputted into unit 202, for example, impedance measurements, ECG, RFgenerator calibration, and/or vagus nerve stimulation (VNS) signals.

Optionally, connector 902 (and/or unit 202) includes circuitry and/orcode implementable by a processor, to detect, test, and/or record acatheter specific feature that characterizes the coupled catheter (e.g.,off-the-shelf catheter), for example, the feature is mapped to a recordin a database (or look-up table or other data structure) representingdata of the catheter. The coupled identified catheter may be calibrated,for example, the position of the catheter may be calibrated as describedherein. Calibrated data may be stored (e.g., locally on connector 902and/or unit 202). Data transmission between connector 902 and unit 202may be encrypted.

Connector 902 may be designed for single use (e.g., disposable), forexample, made out of relatively inexpensive materials, and/or providedsterilized.

It is noted that one or more interfaces 210, 218, 212, 226, 230, 234,242 may be implemented, for example, as a physical interface (e.g.,cable interface), and/or as a virtual interface (e.g., applicationprogramming interface). The interfaces may each be implementedseparately, or multiple (e.g., a group or all) interfaces may beimplemented as a single interface.

Processor 204 may be coupled to one or more of program store 206, datarepository 208, and interfaces 210, 218, 212, 226, 230, 234, 242.

Optionally, system 200 includes a data repository 208, for example, forstoring the dataset (e.g., imaging data of a patient), the simulation,received electrical and/or thermal parameters, and/or other data (suchas: health record of a patient). The data may be displayed to a user(e.g., physician) before, during and after the procedure.

It is noted that one or more of processor 204, program store 206, datarepository 208, and interfaces 210, 218, 212, 226, 230, 234, 242 may beimplemented as a computing unit 202, for example, as a stand-alonecomputer, as a hardware card (or chip) implemented within an existingcomputer (e.g., catheterization laboratory computer), and/or as acomputer program product loaded within the existing computer.

As described herein, program store 206 may include code implementable byprocessor 204 that represents a simulation tool and/or application thatgenerates RF simulations (e.g., based on simulated generated fields)based on a provided dielectric map and/or other data.

Referring to FIG. 1, at 102, a dataset of a body portion of a patientincluding anatomical imaging data of the patient (optionally 3D data) isprovided, for example, acquired from imaging modality 211 (e.g., CT,MRI), retrieved from repository 208, and/or acquired from an externalserver or other storage. Alternatively or additionally, the dataset isacquired and/or derived from a functional imaging modality, for example,NM and/or SPECT. For example, data from the NM modality may be used toinfer the location of autonomous nervous system components (e.g., one ormore GPs) designated for treatment on the dataset from the CT modality,for example, as described with reference to “BODY STRUCTURE IMAGING”,International Publication No. WO/2014/115148 filed Jan. 24, 2014,incorporated herein by reference in its entirety.

The data obtained from the CT machine (and/or other imaging devices) mayserve as a basis for geometrical structure and/or modeling of internalorgans of the patient, for example, the organs are segmented using imagesegmentation code. The electrical and/or thermal properties and/or othervalues (e.g., mechanical, physiologic, other tissue related values) areassociated with each organ, optionally according to the designatedoperational frequency used by the RF ablation catheter.

Optionally, the imaging dataset includes the target tissue for treatmentin a catheterization procedure, for example, the heart. Optionally, theimaging dataset includes tissues surrounding the target tissue forsimulation of the procedure, for example, a full body scan, a fullthorax scan, a chest and abdominal scan, and/or a chest scan. Forexample, for an intra-cardiac ablation procedure, a full thorax scan maybe performed.

Optionally, the imaging dataset is analyzed and/or processed to identifydifferent types of tissues within the imaging data, for example, eachpixel data or region is classified into a tissue type. Suitableclassification methods include, for example, according to imagesegmentation methods, according to a predefined imaging atlas, and/orbased on Hounsfield units.

Code stored, for example in program store 206, implementable byprocessor 204 accesses estimated dielectric and/or thermal parametervalues, and associates each tissue type and/or pixel and/or region inthe dataset with the estimated dielectric and/or thermal parametervalues. Optionally, the provided imaging dataset includes the associateddielectric and/or thermal parameter values.

The dielectric and/or thermal parameter values may be obtained, forexample, from a publicly available database (e.g., on data server 222),and/or calculated from a model, and/or empirically measured values froma sample of patients. It is noted that the estimated dielectric and/orthermal parameter values may reflect values that have not necessarilybeen measured for the patient being treated. In some embodiments, a 2Dor 3D dielectric map and/or thermal map of the region (e.g., organ) or aportion of the organ is created and optionally displayed to a user.

The dataset including anatomical image data associated with thedielectric and/or thermal parameter values may sometimes be referred toherein as a dielectric map and/or thermal map. The dataset sometimesincludes both the dielectric map and the thermal map. The datasetsometimes includes one of the dielectric and thermal maps. It is notedthat the dielectric map may include dependencies of the dielectricparameter values on the thermal parameter values. The dielectric mapinformation and the thermal map information may be displayed on the samemap.

As used herein, the term dielectric map sometimes includes both thedielectric map and the thermal map. As used herein, the term dielectricmap may sometimes be interchanged with the term thermal map.

Optionally, the anatomical image (e.g., after segmentation) and theestimated dielectric and/or thermal parameter values or the 2D or 3Ddielectric map are inputted to the simulation tool, which may beimplemented as code stored in program store 206 implementable byprocessor 204, or as a separate unit (e.g., external server, hardwarecard, remotely located code implementable locally).

Optionally, the dataset is used to generate a simulation as part of apre-planning phase, for example, as described with reference to FIG. 3.The pre-planning phase simulates different parameters for the plannedprocedure, to help select one or more different parameters for theactual procedure, according to, for example, reduced error in trackingthe location of the catheter, improved accuracy in tracking location ofthe catheter, selection of the treatment location of the catheter,and/or selection of ablation parameters and/or ablation lines accordingto a simulation of the ablation.

Ablation parameters may include one or more of: ablation power and/orduration, frequency of applied signal, angle of catheter, phase valuesbetween pairs of electrodes (e.g., when the catheter includes pluralityof electrodes), electrodes to which a signal is applied, pressureapplied by the catheter, order of ablation points along the ablationline and/or any other parameters that may affect the ablation procedure.

Optionally, a forecast success rate of treatment parameters (ablationparameters, treatment location, ablation method etc.) or selectedcatheter model(s) may be presented to the user. The user may selecttreatment parameters and/or catheter model(s) based on the forecastsuccess, e.g., to obtain maximum success. For example, the cathetermodel(s) may be selected according to the simulation, for example, toreduce cross-talk between catheter models. In another example, theablation location may be selected, for example, according to asimulation ablation having an estimated success rate of 85%. In yetanother example, the placement of multiple catheters may be selectedaccording to the simulation, for example, to improve the treatment ofthe procedure. In yet another example, the administration of drugs maybe selected according to the simulation, for example, the type of salinebeing administered, the timing of the patient medication, and/or theadministration of other drugs, for example, to improve transmission ofelectrical fields through the body of the patient. In yet anotherexample, the patient's medical condition may be considered by thesimulation in planning the treatment, for example, the presence ofcalcification deposits, tumors, or other anatomical abnormalities may beavoided or considered. In yet another example, the selection ofmechanical force may be performed according to the simulation, forexample, to help avoid injury to nearby tissues the applied force may besimulated. In yet another example, the selection of thermal intervention(e.g., hyperthermia, freezing) may be selected, for example, to improvetreatment. In yet another example, the selection of signals transmittinginto the body or out of the body may be selected, for example, thesignal transmission maybe gated or synchronized with the applied RFenergy and/or sensor measurements to avoid interference.

The operator may update the procedure plan according to the simulation,such as selection of a different catheter to reduce cross-talk.

Optionally, the dielectric parameters include an impedance and/orconductive value of the respective tissue and/or tissue region.

It is noted that the patient may undergo imaging before thecatheterization procedure, for example, as a separate outpatientprocedure.

Optionally, the dataset includes the imaging data and the one or moredielectric and/or thermal parameter values corresponding to differenttissues and/or regions of the anatomical imaging data. The dielectricand/or thermal parameter value represents an initial estimated value,which may be adjusted based on real-time measurements obtained from thepatient, as described herein.

Optionally, the dataset is associated with additional data, for example,mechanical parameters (e.g., fibrosis map, for example, as describedwith reference to block 118), physiological parameters (e.g., patientECG patterns, patient body temperature), and other tissue specificparameters.

Optionally, the dataset is associated with additional data related tothe medical state of the patient, for example, medications the patientis taking (e.g., which may affect the ionic concentration of the tissuesof the patient, affecting the electrical and/or thermal parameters), themedical state of the patient (e.g., which may affect the anatomy of thepatient), and a history of previous treatments (e.g., which may helppredict the effects of the current treatment).

At 104, according to some embodiments, code stored in data repository208 processes the dielectric and/or thermal map (i.e. dataset) of block102, to generate a simulation. The simulation simulates the navigationpath during the procedure or part thereof, using a simulated catheter,and simulated applied electric parameters by simulated extra-bodyelectrodes (e.g., positioned on the skin of the patient). The simulationmay be electro-magnetic (EM) simulation and/or thermal simulation.

Optionally, the simulation receives one or more of the following inputs,to generate the initial simulation and/or update the simulation (e.g.,as in block 114): the anatomical model (e.g., obtained based on a CTand/or other imaging data of the patient), the dielectric map and/orthermal (initial or updated) which includes dielectric properties and/orthermal properties, fibrosis data (e.g., fibrosis map, for example, asdescribed with reference to block 118), conductance map includingacquired anatomical imaging data of the patient and at least oneconductance parameter value corresponding to one or more differenttissues identified within the anatomical imaging data (e.g., from astored location based on previous conductance mapping and/or real-timemapping), ablation catheter parameters (e.g., frequency, model, type,angle of catheter), impedance measurements, thermal propertymeasurements, and/or other data values (e.g., as described herein).

The simulation may track the position (such as coordinates) of thesimulated catheter within the dataset representing the body portionaccording to the simulated application of the electrical fields (orother electrical parameters, such as current, impedance, and/or voltage)within the body portion (e.g., based on the extra-body simulatedelectrodes). The simulation may simulate the measurements of thesimulated applied electrical fields, optionally as measured byelectrodes at a distal portion of the simulated catheter.

Optionally, the generated simulation includes a dataset of thecoordinates (or other position data) of the simulated catheter withinthe dataset related to navigation of the catheter as part of theprocedure.

Optionally, the simulation is performed at one or more operatingfrequencies, for example, when simulating a catheter ablation procedure.Exemplary simulation frequencies include: about 460 kHz, about 1megahertz (MHz), about 12.8 kHz, or other frequencies. The simulationfrequency is used to measure changes during the ablation process, andcorrect the ablation parameters accordingly, as described herein.

Optionally, the simulation includes coordinates in space which representa simulation of electrodes and/or sensors that provide measurements ofvalues of the electrical and/or thermal properties. The simulation ofthe measured values may be used, for example to simulate the measurementof induced currents. The simulation of the induced currents may reducethe number of time the simulation is run to below the number of samplingpoints in space, which reduces the required computational resources toperform the simulation.

Optionally, the simulation calculates the optimal position for amulti-electrode phased RF catheter, for example, to obtain the bestreal-time measurements, for example, with improved signal to noise, orreduced error.

Exemplary commercially available simulation tools that may be used as aframework for generating the simulation described herein include:Sim4Life (available from Zurich Med Tech), COMSOL Multiphysics®, and CSTDesign Studio™.

Reference is now made to FIG. 12, which is a flowchart of an exemplarymethod for generating the thermal component of the generated simulation,in accordance with some embodiments of the present invention.

In some embodiments, at 1202, the dataset of electric properties of thecatheterization procedure materials are set based on the receivedvalues, for example, for a certain catheter, at a certain angle,pressure, and operating frequency (e.g., when performing an ablationprocedure and/or as part of a measurement process). The electricproperties of the catheterization procedure materials may include thedataset of a body portion of a patient including anatomical imaging dataof the patient (optionally 3D data). The dataset may include theassociated dielectric parameter values.

In some embodiments, the simulation is generated to simulate theelectromagnetic fields on the catheter. In some embodiments, the powerdensity loss (PLD) pattern is simulated.

In some embodiments, at 1204, the thermal properties of the tissuesand/or catheterization procedure are set based on the received values.The PLD pattern may be used as a heat source for generating the thermalproperty component of the generated simulation. The thermal propertiesmay be simulated over a period of time to obtain a temperaturedistribution pattern over the period of time, for example, based on theprocedure. The period of time may represent a significant period oftime, for example, based on cardiac output, based on the estimated timeto navigate the catheter within the heart, and/or based on the time forperforming an ablation.

The initial electrical and thermal property values are updated as afunction of temperature based on the initial simulation.

In some embodiments, at 1206 and 1208, blocks 1202 and 1204 are iteratedone or more times. During each iteration, the simulation may use thevalues calculated using the earlier simulation, to improve the accuracyand/or resolution of the updated simulated values. The blocks may beiterated until a stop condition is met, for example, a desired accuracyand/or simulation, and/or until the values remain unchanged within atolerance requirement.

Referring now back to block 104 of FIG. 1, optionally, the generatedsimulation includes determination of a power loss density pattern. ThePLD pattern may be generated for the tissue targeted for (or currentlybeing) treated using RF energy. The PLD pattern may be estimated in timeand/or space. Alternatively or additionally, the simulation includesdetermination of a temperature pattern. The temperature pattern may begenerated for the tissue targeted or (or currently being) treated usingRF energy. The PLD pattern may be estimated in time and/or space. ThePDL pattern may be calculated for multiple points, for each set ofelectrode location (e.g., using the coordinates according to theexternally applied electromagnetic field), the pressured applied to thetissue wall, and the angle of the electrode relative to the tissue. ThePLD pattern may be used in the generated simulation to guide theablation treatment.

The PLD pattern, and/or gasification transition pattern, and/ortemperature pattern may be used to update the simulated electric fieldsfor correction of coordinates determined using real-time measurements ofthe externally applied electric fields. The PLD pattern, and/orgasification transition pattern, and/or temperature pattern may affectthe electric and/or thermal properties of tissues, which may alter thereal-time measurements of the electric field and/or real-timemeasurements of the dielectric, electric, and/or thermal properties.

The PLD pattern, and/or gasification transition pattern, and/ortemperature pattern calculated as part of the generated simulation mayuse the corrected catheter coordinates (and/or simulated cathetercoordinates, and/or measured catheter coordinates) as input of thelocation of the catheter.

The PLD pattern may be calculated using equation (1):PLD=½(σ+ωε_(o)ε^(n))|E| ²=½σ_(e) |E| ²

where:

|E| denotes the magnitude of E,

Ω=2ωf, where f denotes the operating frequency in hertz (Hz),

σ_(e) denotes an effective conductivity defined as σ+ωε_(B)ε_(ε) ^(n).

The temperature pattern may be calculated based on an estimation of therise of temperature, which may be estimated according to the continuityequation (i.e., equation (2)) that describes the simple case ofelectromagnetic heating where the temperature rises at a uniform rate:

$\frac{\partial T}{\partial t} = {{{PLD}/\rho}\; c_{p}}$

Where

ρ denotes the density, and

c_(p) denotes the specific heat.

Reference is now made to FIG. 13A, which is a graph depicting thecalculated PLD pattern created by an electrode 1302 (e.g., RF ablationelectrode(s)) in a tissue 1304, in accordance with some embodiments ofthe present invention. The PLD pattern may be calculated using equation(1). The PLD pattern may be used in the generated simulation describedherein.

D denotes the ablation depth,

G denotes the gap (generally, D+G represents the wall thickness of thetissue),

V denotes the volume of ablated shape. Generally, the top view of anexemplary ablation region has an ellipse type shape. The ablation volumemay be denotes by:

L denotes the length of the ablation region, and

W denotes the width of the ablation region.

Reference is now made to FIG. 13B, which is a graph depicting thecalculated temperature pattern (in degrees Celsius) created by anelectrode 1306 (e.g., RF ablation electrode(s)) in a tissue 1308, inaccordance with some embodiments of the present invention. Thetemperature pattern may be calculated using equation (2). Thetemperature pattern may be used in the generated simulation describedherein.

Optionally, the Gasification Transition (GS) of ablation using cryogenicenergy at each possible ablation region is calculated. The GS may becalculated based on the location of each ablation region, the pressure,the angle of the catheter, and/or other values. Based on the generatedsimulation, the location, pressure, angle, and/or other values may beselected to achieve safe GS values, for example, according to a safetyrequirement.

Reference is now made to FIG. 3, which is a flowchart of a method forselecting one or more parameters for tracking the position of anintra-body catheter, in accordance with some embodiments of the presentinvention. The method may be used as part of a pre-planning phase,optionally executed off-line before the patient undergoes the procedure,for selection of parameters to use during the procedure. The method mayselect one or more of the electric and/or thermal parameters and/or theelements for generating the electric and/or thermal parameters based onthe simulation. The parameters and/or elements may be selected to reducethe error in accuracy of calculating the coordinates of the distal endof the catheter, and/or to improve the accuracy thereof.

Alternatively or additionally, the method may select catheters for usein combination, such as selecting the combination of catheters to use,or selecting one catheter given another catheter is fixed. The cathetersmay be selected to reduce cross-talk, based on reducing the error inaccuracy and/or improve the accuracy of calculating the coordinates ofone or both catheters.

The method may select one or more of the following parameters: theplacement position (e.g., location, angle) of one or more catheters, theadministration and/or time and/or dose of drugs, the application of amechanical force (e.g., to the tissue, as part of the treatment, or partof the navigation), the application of thermal intervention(s), and/orthe timing and/or properties of signals transmitted into and/or out ofthe body.

For example, in terms of drug administration, free electrons serve ascharge carriers, inside tissue ions (e.g., Na+, K+, Cl−) carry theelectric current. Drugs that change blood volume and/or ionic channels,as well as dehydration, volume overload, hypernatremia, and hyponatremiaaffects the efficiency of RF ablation. Such effects may be simulatedusing the generated simulation and tested to select the optimal drugadministration parameters (e.g., dose, timing of administration, type ofdrug). In another example, irrigation ablation catheters may load thepatient with excessive fluids causing dilution and over-hydration. Sucheffects may be simulated over time and considered in the procedure(e.g., regions ablated 30 minutes after procedure start will behavedifferently than ablation of regions at the beginning of the procedurewhen fluids and/or other drugs are administered during the 30 minutes).

The method of FIG. 3 may be executed by system 200 of FIG. 2, forexample, instructions to execute the method may be stored in programstore 206 for implementation by processor 204.

At 302, the simulation may be executed (or re-executed) including avariation of one or more parameters.

Optionally, one or more parameters of one or more of the extra-bodyelectrodes, are varied, for example, extra-body electrode location, sizeof transmitting electrode surface area, geometry of transmittingelectrode surface area, electric field strength, electric currentamplitude, and frequency of electric current.

Alternatively or additionally, the one or more parameters include one ormore other simulated catheters (or of all simulated catheters), whichmay be based on off-the shelf existing EP catheters. Each catheterincludes electrodes at a distal portion thereof that result in cathetercross-talk, which may reduce the accuracy of calculation of thecoordinates of the distal end of each catheter.

Alternatively or additionally, one or more other parameters are set, forexample, the placement of multiple catheters, the administration ofdrugs (including saline), the presence of disease, the effects ofprevious treatments, the application of mechanical force, theapplication of a thermal intervention, and the application of signal(s)transmitted to and/or from the inside of the body of the patient.

At 304, the code may estimate an inaccuracy in the simulationcoordinates, and/or estimates the resolution of accuracy of thecoordinates, based on the varied parameters. Alternatively oradditionally, the code estimates the inaccuracy and/or the resolution ofaccuracy of the simulation coordinates for each simulated catheter inview of cross-talk between the catheters.

Optionally, the error and/or accuracy is estimated when the catheter(s)is in proximity to the target tissue (as that is where the highestaccuracy may be desired).

At 306, blocks 304 and 302 are repeated, by varying the value of theparameter and re-executing the simulation (completed or partial) toestimate the accuracy and/or error in accuracy using the variation.Alternatively or additionally, the combination of catheters is varied.

Calibration may be iteratively performed to correct, for example,between the simulation dielectric and/or thermal space and the actualmeasured dielectric and/or thermal space. The calibration may correctfor scaling and/or shifting differences, or other variations between thesimulation and the real world. Optionally, a database of simulatedvalues may be created and/or used to store previously calibratedsimulation results. The previously calibrated simulation results may bere-used, for example, in another procedure of the same patient, toreduce the processing resources required to generate the simulation, bypreventing or reducing the re-calibration.

At 308, the code may select the values of the varied parameter to reducethe inaccuracy and/or achieve the highest accuracy. Alternatively oradditionally, the code selects the combination of catheters to reducethe accuracy error and/or achieve the highest accuracy in view ofcross-talk. The code may select one or more of: the position placementof each of multiple catheters, the timing, concentration, and/or type ofdrug administered, the position and/or magnitude of the appliedmechanical force, the position and/or temperature profile of the thermalintervention, and the strength, pattern, frequency, amplitude, and/ortiming of signal(s) transmitted to and/or from the inside of the body ofthe patient.

Different results may be presented to the user (e.g. on display 232), toallow the user to select which treatment parameters and/or elements touse and/or catheters. For example, the code may select a size of theextra-body electrodes and/or catheter model that may not be in stock, inwhich case an alternative may be selected that is in stock to try andobtain similar accuracy. In other examples, the results presented to theuser may include, for example, different positions for the multiplecatheters, different drugs that may be administered and/or the timing ofthe dose, different possibilities for application of the applied force,different temperature profiles of thermal interventions, ablationparameters, and signal patterns for transmission into and/or out of thebody.

The selection may be done in advance of the procedure, such as to allowobtaining the selected equipment. When the code selects the location forthe extra-body electrodes, the skin of the patient may be manuallymarked (e.g., with a marker) in advance, for placement of the extra-bodyelectrode during the procedure.

Referring now back to FIG. 1, at 106, the physical position of aphysical catheter during the real catheterization procedure may betracked, as the catheter is navigated inside the patient. Optionally,the physical tracking is based on impedance based mapping techniques, asdescribed herein. It is noted that blocks 102 and 104 may occur offline,before the procedure has started.

Optionally, code stored in data repository 208 implementable byprocessor 204 of system 200 physically tracks coordinates of theposition of the distal portion of the physical catheter within thephysical body portion of the patient. The coordinates may be calculatedaccording to physically applied electrical fields within the bodyportion and measurements of the electrical fields performed byelectrodes 214 and/or sensors 228 at a distal portion of physicalcatheter 216 received via interface 212 and/or 226.

Alternatively, coordinates are provided to processor 204, calculated bynavigation system 236 (e.g., impedance measurement based navigationsystem as described herein) via interface 234.

At 108, the code implementable by the processor(s) may register thephysically tracked coordinates with the simulation coordinates. Theregistered coordinates may be analyzed to identify differences betweenthe physically tracked location coordinates and the simulationcoordinates.

The differences may include differences in absolute coordinate values.The differences may include differences in coordinate values consideringan error in accuracy reading, for example, partial or lack of overlap inthe coordinate values considering the margin of error in accuracy forthe value. The difference may include differences in estimated precisionof the coordinate values, for example, the physical coordinates accurateto within about +/−2 mm (millimeters) and the simulated coordinatesaccurate to within about +/−1 mm.

Optionally, the simulation location coordinates are calibrated accordingto a defined anatomical and physical location of the distal end portionof the physical catheter. For example, the user may manually mark on thescreen displaying the simulated image of the dataset, the locationcorresponding to knowledge of the user (e.g., based on anatomicalknowledge and catheter operation experience), for example, within theleft atrial appendage. In another example, the code analyzes themovement of the catheter to detect physical locations within thesimulated dataset image (e.g., displayed on the screen), for example,the catheter trapped within a cone shaped structure may indicate theapex of the left atrium. The calibrated simulation coordinates may beregistered to the physical coordinates based on the registration. It isnoted that the calibration of the simulation coordinates may occuriteratively to update the dataset, which may improve accuracy of thesimulated coordinates, for example, as described with reference to block114.

Alternatively or additionally, other calibration methods may be used,for example, when the physical catheter includes multiple electrodeswith predefined known distances between the electrodes, the knowndistances may be used to calibrate the physical coordinates.

At 110, code implementable by the processor may correct the physicallytracked location coordinates according to the registered simulationcoordinates. For example, when the registered coordinates haveoverlapping ranges (considering the error in accuracy), with thesimulation coordinates having lower error than the physical coordinates,the physical coordinate may be corrected to have the error range of thesimulation coordinates. In another example, a weighing algorithm maycalculate the corrected coordinates by assigning a calculated weight tothe simulated coordinates, and correcting based on the weightedsimulated coordinates.

At 112, code implementable by the processor may provide the correctedphysically tracked location coordinates for presentation on display 232via output interface 230. Alternatively or additionally the correctedcoordinates may be forwarded to an external server, stored (locally orremotely), and/or undergo further processing (e.g., as describedherein).

At 114, one or more of blocks 104, 106, 108, 110, 112, 116 (as discussedbelow) and 118 (as discussed below) are iterated.

Optionally, the iterations are performed until a stop condition is met,for example, identification of a template of signals that is indicativeof achievement of a target, for example, indicative of achievement of adesired ablation pattern. The template may be created for each patient,a group of patients having one or more common characteristics, or ageneral template for all patients being treated. Exemplary stopconditions include the achievement of, for example, tissue coagulation,tissue edema, transmural ablation, continuous ablation line, and otherindicators that are associated with effectiveness of the ablationprocedure and/or safety of the ablation procedure. The template may bebased on measured electrical and/or thermal properties described herein,and/or other sensed signals, for example, intravascular ultrasoundimaging. Multiple templates may be available, for example, representingthe desired ablation pattern. Template may be available representingpartial achievement of the target ablation pattern, for example, about25%, about 50%, or about 75% ablation achievement. The received signalsmay be correlated to identify the template with the highest correlation,and/or according to a correlation requirement representing similaritywith the template. The template(s) may be created by applying one ormore machine learning methods to experimentally collected and/orsimulation generated data, for example, a statistical classifier may betrained to receives as input the sensed signals and generate an outputof a category indicative of the achievement or lack of achievement ofthe desired ablation pattern. It is noted that the term template as usedherein may mean a set of signature signals used by machine learningmethods represented using the relevant data structure of the machinelearning method.

Optionally, the iterations update the displayed location of the catheterwithin the displayed patient images on the screen, for example, as thecatheter is navigated inside the body of the patient.

Optionally, the accuracy of the simulated coordinates is improved by theiterations, as described herein. Optionally, the iterations areperformed to achieve a desired accuracy, for example, a target rangeand/or threshold. The target accuracy may be less than the accuracy ofthe measured physical coordinates. Optionally, the accuracy target isabout +/−1 millimeter for the corrected physically tracked coordinates.

It is noted, that the physically tracked coordinates (non-corrected) mayhave an accuracy of about +/−3-5 mm, or about +/−2 mm. Improving thecorrected coordinates to an accuracy of about +/−2-3 mm, or about +/−1mm may allow, for example, for improved precision in targeting GPs.Accuracy may be defined, for example, as an average error over themapping volume (e.g., the full volume, or the sub-volume). In anotherexample, accuracy may be defined as the true error between theanatomical landmarks, and/or the true error between ablations atdifferent cardiac regions.

Reference is now made to FIG. 4, which is a flowchart of a method ofiteratively updating a simulation of the position of an intra-bodycatheter, in accordance with some embodiments of the present invention.The method of FIG. 4 may be executed in real-time, during the procedure,based on real-time measurements acquired from the body of the patientduring the procedure. The method of FIG. 4 may be executed by processor204 implementing code stored in program store 206. The time interval forupdating the simulated electrical and/or thermal properties is, forexample, every about 1 second, or every about 5 seconds, or every about10 seconds, or within the range 3-10 seconds. The resolution timeinterval may be preset (e.g., constant), or dynamically selected, forexample, updated at a lower frequency when the catheter is far from thetarget, and updated at a higher frequency when the catheter is closer tothe target.

It is noted that for computationally intensive and/or complicatedsimulations, the simulation does not necessarily need to be entirelyre-calculated during every iteration. An initial base data set used bythe simulation may be generated and stored, for example, in a database(e.g., based on electromagnetic and/or tissue parameter analysis ofpossible ablation points in a defined ablation space). For each point,for each predefined internal of time (e.g., every about 1-10 seconds),electric and/or thermal parameter values may be calculated (e.g.,voltage, current, impedance, optionally in vector format) and used toupdate the generated base dataset. In real-time, correlations may befound between the measured electrical and/or thermal parameter valuesand the base dataset values. The correlation may be used to update thegenerated simulation in real-time, which may improve performance of thecomputing unit updating the generated simulation, for example, byreducing the time and/or processing resources used to updated thegenerated simulation.

At 402, the code may receive a real-time measurement of one or moredielectric and/or thermal parameter(s) of one or more intra-bodytissues, for example, via sensor interface 226 and/or electrodeinterface 212.

The dielectric parameter(s) may be impedance and/or conductivity.Optionally, the dielectric parameters correspond to the dielectricparameters associated with the imaging data of the dataset.

Optionally, one or more additionally measured electrical properties arereceived and used to update the simulated dielectric parameters, forexample, current, and voltage. It is noted that commonly availablecatheters and/or commonly available sensors may be used, for example,voltage may be measured, from which the other dielectric parameters maybe calculated or estimated.

Optionally, the impedance of the myocardium (and/or other tissues)includes the real and/or imaginary components. Optionally, the impedanceis acquired in at least two frequencies. Impedance measurements may beperformed substantially concomitantly, such as simultaneously orsequentially for each frequency with relatively short and/orinsignificant delays between the measurements.

Optionally, the impedance of the myocardium (and/or other tissues) ismeasured at a frequency selected as being away from existing commercialintra-cardiac ECG recording system filters, to prevent and/or avoidinterference with the ECG recordings (to the ECG and/or to the impedancemeasurement), for example, about 20-100 kilohertz (KHz), or about 40kHz. Alternatively or additionally, the impedance of the myocardium(and/or other tissue) is measured at a frequency selected as being awayfrom existing RF generating system (e.g., ablation system) and/or fromfolding frequencies thereof, optionally at least 500 kHz away, toprevent and/or avoid interference with the RF ablation system (to the RFablation and/or to the impedance measurement), for example, 1 megahertz(MHz), which may be selected for measuring frequency and/or accuratelyseparating between healthy tissues and/or between healthy and malignantsamples, and/or for helping to distinguish between fibrotic tissue andviable myocardium.

Optionally, individual calibration per catheter (as described herein)and/or simulation of the catheters (as described herein) is performed,before and/or during measurement of the myocardial impedance. Thesimulation and/or calibration may improve accuracy of the measurement,by accounting for and/or correcting parasitic capacitance and/or crosstalk that occur along long catheters and/or connection cables, asdescribed herein.

The intra-body tissue may be blood. The blood dielectric and/or thermalparameter may be measured, for example, by an indwelling catheter,and/or by retrieving blood samples for analysis in an external machine.Blood flowing past the treatment elements of the catheter may be heatedwhen the catheter is applying energy, for example, during an ablationprocedure. As such, correcting the coordinates to account for changes inblood flow dielectric and/or thermal parameters due to the heatingeffect may improve the accuracy of the coordinates.

The intra-body tissue may include the target tissue and/or nearbytissue, such as the tissue targeted for ablation, for example,myocardium (e.g., when the heart is being treated), tumor tissue, neuraltissue (e.g., when epicardial ganglionated plexi are being ablatedand/or blocked) or other tissues being treated. The dielectric and/orthermal properties of the myocardium may be measured, for example, bythe catheter described with reference to FIGS. 8A-C. The target tissueand/or nearby tissue may be heated when the catheter is applying energy,for example, during the ablation procedure. As such, correcting thecoordinates to account for changes in tissue dielectric and/or thermalparameters due to the heating effect may improve the accuracy of thecoordinates.

Other electrical properties of tissues (e.g., blood, bone, lungs, heart)that may be measured include relatively permittivity and/orconductivity. Optionally, the electrical properties are measured at theoperating frequency (or frequencies). The measurement at one or morefrequency may be used to estimate losses occurring at each frequency.Other exemplary electrical properties that may be measured to estimatethe reaction and/or changes to the applied electric fields used tonavigate the catheter includes voltage, and current (complex and/orabsolute values).

Alternatively or additionally, additional data is gathered in real-time,and used to update the generated simulation. For each data item,deviations from the simulated data item may be calculated and used toupdate the simulation, e.g., to better reflect actual procedureconditions. The additional data may affect the electric and/or thermalproperty values of the tissues, for example, in simulating the locationof the catheter, simulating the effect of application of force by thecatheter to the tissue, and/or simulating the ablation treatment.Updating and/or correction of the additional data may improve thesimulation based on the electric and/or thermal property values of thetissues. The additional data may be manually entered by the operator(e.g., patient weight), obtained from an interface to one or moreexternal devices that perform measurements (e.g. blood pressuremachine), obtained from sensors (e.g., catheter temperature), and/orobtained by accessing an external data source, such as a database (e.g.,patient medications from an electronic medical record).

Exemplary additional data gathered in real time include one or more of:

-   -   Catheter potential—may be used to update the simulated catheter        potential.    -   Body surface potential—may be used to update the simulated body        surface potential (e.g., for correcting the electric fields used        to guide the catheter).    -   Catheter temperature—may be used to update the simulated        catheter temperature, when the catheter is delivering ablation        treatment, and/or when the catheter stopped the treatment.    -   Patient weight and/or blood pressure—may be used to improve the        simulation of the deformation of the tissue as a reaction to        force applied by the catheter's distal end on the tissue, such        as during ablation treatment. The patient's weight and/or blood        pressure may reflect pre-existing internal mechanical forces        being applied to the tissue. The deformation affects the        electric field values and the resulting simulated temperature        pattern of ablation.    -   Pressure applied by the distal end of the catheter to the        tissue—may be used to improve the simulation of the deformation        of the tissue.    -   Catheter irrigation rate—may be used to improve the estimation        of the boundary conditions around the simulated distal end        region of the catheter. The catheter irrigation rate affects the        electric field values and the resulting simulated temperature        pattern of ablation.    -   Drug administration—may be used to improve the estimation of the        electric parameter values of the tissues, due to ionic effects        of the drugs and/or saline. The electric properties of cells are        affects by certain drugs and/or fluids.    -   ECG—may be used to improve the estimation of the electric        parameter values of the tissues. The electrical activity of the        heart may dynamically alter the electric parameter values of the        tissues, which may be incorporated into the simulation.    -   Energy application data—may be used to estimate the amount of        applied power that is absorbed (e.g., by flowing blood), such as        over a period of time. The absorption of energy affects the        energy required to perform the desired ablation treatment.

Optionally, real-time measurements of the electric fields generated bythe externally located body patches (also referred to herein asextra-body electrodes) are performed in response to an injected signal.Optionally, the injected signal, for example, a voltage pattern, acurrent pattern, or other signal pattern, is applied to the bodyelectrode patches located externally to the body of the patient (i.e.,the patches used to create the electric fields which are used to helpnavigate the electrode). The injected signal may be superimposed on theelectric fields. The injected signal may be sensed by the sensors on thedistal portion of the electrode used to sense the applied electricfield. An analysis may be performed, to compare the sensed injectedsignal to the applied injected signal. The analysis may determine thecorrection to be applied to the coordinates determined used the electricfields. The correction based on the injected signal may improve theaccuracy of the generated simulation.

The signal may be injected before the ablation, during the ablation,and/or after the ablation. The ablation process may change the electricand/or thermal property values of the tissues in proximity to thesensors on the distal end of the catheter. As such, without correction,the sensors may sense a change in location of the catheter using theexternally applied electric fields due to the change in the tissueelectric and/or thermal property values, even when the catheter remainssubstantially in the same position. The analysis of the injected signalmay correct the measurements of the externally applied electric fields,to correct the coordinates as the ablation proceeds, and avoid orprevent errors due to the change in tissue electric and/or thermalproperty values due to the ablation.

Optionally, at 404, the code may receive a selected sub-volume for theiteration. The sub-volume may be selected from the dataset,automatically and/or manually. The sub-volume defines the region for theupdate of the simulation in the iteration. Updating the sub-volumeinstead of the entire (or larger) dataset may allow for fasteriterations and/or using fewer computing resources. For example,generating the entire simulation may require 30 minutes using a certainprocessor, which each iteration may be performed in 30 seconds using thesame processor for a relatively small sub-volume.

Sub-volumes may be manually selected, for example, by the user drawing abox (or other shape) on the display, defining the sub-volume within thedisplayed anatomical image.

Alternatively or additionally, the sub-volume may be automaticallyselected by the code, optionally based on a volume (e.g., box) thatincludes the target tissue in near proximity to the distal end of thephysical catheter.

Optionally, the iterations are performed with decreasing volumes of thesub-volume, optionally automatically, as the distance between the distalend of the physical catheter and the target tissue decreases (e.g., asthe operator navigates to the catheter to the target tissue). In thismanner, the accuracy of the position of the catheter may automaticallyincrease with the iterations as the catheter is being navigated towardsthe target tissue. Increasing accuracy may be needed to guide thecatheter to the target. For example, during introduction of the catheter(e.g., within the femoral artery) an accuracy of about +/−5 mm may beobtained (which may be sufficient within the femoral artery), duringnavigation inside the heart chambers an accuracy of about +/−3 mm may beobtained, and during fine navigation to position the ablation electrodesfor ablation, an accuracy of about +/−1 mm may be obtained.

Optionally, the iterations are performed according to the procedurebeing performed. Optionally, the sub-volumes are selected according tochanges in the location of the catheter, for example, as the catheter isperforming an ablation in one spot and moves to a neighboring spot, thenew sub-volume is selected according to the neighboring spot that thecatheter is treating. Optionally, the new sub-volume may include regionsof the previous sub-volume, such as one or more overlapping regions, ormay include the entire previous sub-volume. Inclusion of the previouslytreated region within the previous sub-volume may be used to improvesimulation of the state of the target tissue within the new sub-volume,for example, by accounting for physical changes of the previouslytreated tissue that affect the thermal and/or electrical properties ofthe tissues at the new treatment location.

Optionally, the iterations are automatically performed, for example,during the procedure, for example, according to a predefined period oftime, such as every 1-10 seconds.

At 406, the code may generate an updated version of the simulation byupdating the initial estimated value (or the previous measured value) ofthe dielectric and/or thermal parameter value with the real-timemeasurement. The updated simulation is used to adjust the correctedcoordinates, and/or re-calculated the corrected coordinates. Optionally,the updated simulation is performed for the entire region and not asub-volume, e.g., block 404 may be omitted.

The simulation may be updated according to real-time data associatedwith a real-time state of the patient during the procedure, for example,one or more of:

-   -   Catheter location—the actual location of the distal end region        of the catheter contacting tissue and/or the angle of the        contacting distal end region relative to the tissue improves the        quality of the simulation of the ablation region.    -   Body electrode patch location—the actual location of each body        patch (which is used to create electric fields used for        navigation of the catheter) may be used to improve the        simulation of the electric fields, which may improve accuracy of        the location of the catheter using the electric fields. Since        different body tissues have different impedance values and/or        differ in electric and/or thermal property values, the actual        location of the patches affects the measurements of the electric        fields performed by sensors on the catheter. The actual location        of the patch may improve the simulation by reducing the error        between the simulated location of the catheter and the actual        location of the catheter.    -   Catheter temperature—may be used to update the simulated        boundary conditions in the thermal parameter component of the        simulation.    -   Catheter sensed pressure—may be used to update the simulated        application of force to the tissue by the distal end portion of        the catheter.    -   Catheter sensed data—may be used to update the simulated        ablation, for example, by updating the simulation according to        the actual operating frequency, which may be different than the        simulated operating frequency.    -   Body patches sensed information (the body patch electrodes may        be used to sense the catheter inside the body)—may be used to        update the simulated location of the catheter and/or to reduce        the error relative to the actual location of the catheter.    -   Ablation energy deposits—may be used to update the simulation        with the actual applied energy and the actual dissipated energy        (i.e., not used to ablate, due to losses into nearby tissue).

Optionally, the generated simulation may be used to guide therapy of theinterventional procedure, for example, ablation using RF energy at oneor more regions using the catheter. Optionally, the generated simulationincludes an estimated PDL of the ablation RF energy at the one or morepoints. The estimated PDL may be determined based on real-time values(e.g., which may be provided in block 402), optionally one or more of:location of the ablation electrode(s) of the catheter (e.g., based onthe coordinates according to the applied electric fields), the pressurethe catheter applies to the tissue and/or the angle of the ablationelectrode.

Referring now back to FIG. 1, optionally, at 116, the extent of theablated target tissue, such as the size (e.g., dimension about parallelto a tissue depth axis), volume, and/or depth (e.g., along the depthaxis) may be estimated by the code implementable by the processor.Alternatively or additionally, the quality of the contact force betweenthe distal end of the catheter and the tissue in contact with thecatheter is estimated by the code implantable by the processor.

Inventors discovered that the measured impedance between an electrode(or sensor) on the catheter (e.g., distal end thereof) and one or moreother electrodes (e.g., on the same catheter, on another catheter,and/or an extra-body electrode) is correlated with desired contactbetween the catheter and tissue (e.g., target tissue and/or nearbytissue). Inventors discovered that although there is a large variance inthe relation between the applied force and the impedances, the varianceof the contact estimation may be significantly reduced by takingmultiple reading samples from different locations of the same tissue,the same organ, and/or from other similar organs (e.g., of livingsubjects, of living mammals, of human cadavers, of slaughtered animals).

Inventors discovered that a set of such measurements, for example, asdepicted in FIG. 10, may serve as a basis to generate a model forestimating contact force according to real-time impedance measurementsin the patient, for example, by generating a trained statisticalclassifier, one or more correlation functions, and/or other learningmethods. The real-time impedance measurements may be complex value,magnitude or imaginary part of the impedance.

Reference is now made to FIG. 10, which is a an example of a graphplotting multiple impedance measurements obtained by an electrode on acatheter, and an associated measured force, useful for generating amodel for real-time force estimation based on real-time impedancemeasurements, in accordance with some embodiments of the presentinvention. A single point on the chart represents a measurement at aspecific location under a given force. Dots 1004 represent the real partof the impedance. Dots 1002 represent the imaginary part. The set ofmeasurements were obtained at different locations of the same organ. Theaverage relation is described by dots 1006, obtained by fitting a modelto the set of points. Note the relatively large variance around theaverage.

A conjecture reached by the inventors for the variability of theimpedance (given a fixed level of force) is that the impedance isdirectly related to variability in the quality of the contact betweenthe tip of the catheter and the tissue. Inventors hypothesize that thecontact is determined not only by the force applied to the tip, but alsoby micro-structured contact which is formed between the catheter tip andthe tissue.

Optionally, the estimated applied contact force is selected from thegroup: suboptimal contact force, optimal contact force, and excessivecontact force.

Alternatively or additionally, another trained machine learning methodis applied to correlate the one or more impedance measurements with anestimated dimension of the ablated tissue lesion, optionally one or moreof: depth, surface diameter, and volume. Optionally, the real-timeimpedance measurements are obtained before the ablation procedure.Alternatively or additionally, the real-time impedance measurements areobtained after the ablation procedure. For example, as shown in FIGS.11A-B, which are example graphs depicting the correlation between anestimate of the depth of an ablated tissue lesion based on impedancemeasurements, and a measured depth, in accordance with some embodimentsof the present invention.

FIG. 11A depicts an estimated depth of the lesion based on pre-ablationimpedance values measured between an electrode of the ablation catheterand one or more other electrodes (e.g., body patch electrodes). FIG. 11Bdepicts an estimated depth based on pre and post-ablation impedancemeasurements.

Referring now back to FIG. 1, alternatively or additionally, one or moreother parameters are estimated based on the dielectric and/or thermalmeasurements (e.g., impedance), for example, temperature of the targettissue and/or nearby tissue, and/or spatial pattern of ablation. Theparameters may be estimated, for example, by machine learning methodsthat receive the dielectric and/or thermal measurements (and/or othervalues), apply a machine learning algorithm (e.g., statisticalclassifier), and output an estimated value. The estimations may beperformed in real-time based on real-time measurements. The estimatedvalues may be outputted to the user, which may aid the operator indeciding on the treatment, for example, whether the desired temperatureis reached and/or whether the desired ablation pattern is beingobtained.

The machine learning methods described herein may be applied to themeasured impedance value by code stored in the program store,implementable by the processor of the computing unit. The machinelearning method (e.g., trained statistical classifier, one or morefunctions, a look-up table, a parametric model, support vector machinewith optional radial basis function, or others) may be implemented bythe code, which may be downloaded, for example, from a central server,and/or locally stored.

The methods described herein may allow for faster estimation (e.g.,close to real-time) of the extent of ablation, for example, as comparedto methods that require additional time to allow edema to resolve.

Reference is now made to FIG. 5, which is a flowchart of a method forestimating volume and/or depth of an ablated lesion, and/or forestimating a contact force applied by the intra-body catheter to thecontacting tissue, in accordance with some embodiments of the presentinvention. The method may estimate the contact force according to one ormore measurements performed of the contacting tissue, optionally theimpedance and/or conductance. Optionally, the method estimates thequality of contact force according to a categorization into one ofmultiple categories, which may be clinically relevant, instead of, forexample, calculating an absolute force measurement.

Optionally, at 502, a thickness of the tissue in contact with the distalend of the catheter, which may include a target tissue for ablation, maybe measured or calculated. The measurement may be performed manually bythe user via the screen and/or user interface or automatically by thecode according to the dataset and position of the distal end of thecatheter. The thickness may be calculated from one or more anatomicalimages of the patient (e.g., left atrial wall thickness—LAWT, may becalculated from a patient's CT image).

The thickness of the tissue may represent the extent of the allowed ordesired ablation. For example, in some cases, transmural ablation acrossthe entire depth may be desired, such as to ablate the entire tissuedepth. In other cases, the ablation is to be performed without reachingthe entire depth, such as to prevent perforation.

At 504, the simulation may be executed (or has been executed in block104) to include a simulated ablation of the target tissue, for example,calculated using a model, based on experimental data, and/or based onthermodynamic equations. The simulation may be of ablation by thesimulated catheter according to the real-time location of the physicalcatheter, and/or the simulation may be performed in advance, of thesimulation location of the simulated catheter.

The simulation of ablation of the target tissue may be part of thepre-planning phase and may be used to select one or more catheters forablation, ablation parameters (for example: ablation frequency and/orpower etc.). The simulation may also provide the user (e.g., physician)with a forecast success criteria of the simulation to enable the user toselect the one or more catheters for ablation, ablation parameters thelike. The process may be iterated until optimal results are obtained.

Optionally, the simulation is an EP ablation, for example, aradiofrequency (RF) ablation procedure.

The simulation may be performed according to a simulated optimal contactforce between the distal end portion of the simulated catheter andtissue in proximity to the target tissue. The simulation may beperformed according to the current estimated contact force (e.g., asestimated herein).

Optionally, the simulation of the ablation is according to one or moreablation parameters (e.g., voltage, current, frequency, and/or ablationelectrode surface area dimensions). The ablation parameters may bevaried (e.g., as described herein) for selection of optimal values, maybe automatically determined, and/or may be selected by the user.

At 506, the code may receive one or more measurements of a dielectricand/or thermal parameter of tissue in proximity to the target tissueand/or including target tissue. The measurement may be of the myocardium(as described herein), and/or of the tissue in contact with the catheterablation electrodes (e.g., by one or more electrodes and/or sensors onthe physical catheter) and/or other tissue (e.g., blood, as describedherein).

Optionally, the measurement(s) is performed iteratively, before anablation of the target tissue, during the ablation, and/or after theablation of the target tissue.

Optionally, the measurements are performed in at least two frequencies,by the same sensor and/or electrode or different sensors and/orelectrodes. The different frequencies may improve accuracy of thereading. The two frequencies may be selected to provide independentmeasurements, without significant interference, and/or interference thatmay be accounted for and removed.

Optionally, at 508, the code may correlate the measured thickness withthe received dielectric and/or thermal parameter to estimate the lesionvolume and/or lesion depth. The correlation may correct the estimatedlesion volume and/or lesion depth. The correlation may be used tosimulation the lesion volume and/or lesion depth.

Optionally, at 510, the code may correlate the measured dielectricand/or thermal parameter(s) to estimate a quality of the contact forcerelative to the simulated optimal contact force. The correlation may beperformed, for example, by a statistical classifier that receives theparameter values and maps the values to one of multiple force qualitycategories, by a function, or other methods. The classifier may bepre-trained, for example, using experimental data and/or simulated data.

Optionally, the estimated quality of the contact force is categorizedinto one of the categories: suboptimal contact force, optimal contactforce, and excessive contact force. The categories may be moreclinically relevant to the operator, for example, relative to absoluteforce measurements. The categories may simply represent to operator ifthe applied force is right, more force is needed, or the force is to bereduced.

At 512, one or more blocks 506, 508, and 510 are iterated, for example,before the ablation, during the ablation, and/or after the ablation.

Reference is now made to FIG. 6, which is a flowchart of another methodfor estimating quality of contact between the intra-body catheter and atissue based on tracking a trajectory of motion of the contactingcatheter portion, in accordance with some embodiments of the presentinvention.

At 602, the code may receive and/or analyze measurements of and/orsimulates motion of pulsating tissue in contact with or in nearproximity to the distal end of the catheter (e.g., the ablationelectrodes) over a time range. The time range may include at least onecardiac cycle, optionally several cycles.

The measurements may be performed, for example, from image data. Thesimulation may be performed based on the simulation dataset.

The tissue pulsates due to the beating motion of the heart.

At 604, the code may analyze the coordinates of the position of thedistal portion of the physical catheter over a time range (optionallythe same range as in block 602), to identify a motion trajectory.

The time range may include one or more cardiac cycles.

Optionally, at 606, the motion trajectory of the distal end of thecatheter and/or the motion of the pulsating tissue may be correlated bythe code to cardiac contractility data, for example, gated to areal-time ECG measurement (which may be obtained using external devicesand/or standard methods).

At 608, the code may correlate the trajectory of the distal portion ofthe catheter with the motion of the pulsating tissue. The correlationmay be performed according to the cardiac contractility data.

At 610, the code may estimate a quality of contact between the distalportion of the physical catheter and the pulsating tissue portionaccording to an analysis of the correlation. Optionally, the analysis isperformed according to the cardiac contractility data. The code mayclassify the quality of contact, for example, according to a statisticalclassifier, a function, or a model.

For example, high correlation of movement between the catheter's distalend and the pulsating tissue that matches with the cardiac contractilitydata may be classified as good quality contact. For example, poorcorrelation of movement between the distal end and the pulsating tissuemay be classified as insufficient contact force (e.g., the distal enddoesn't always touch the pulsating tissue). For example, highcorrelation between the movement of the distal end and the tissue, butpoor correlation with the cardiac contractility data may be classifiedas excessive force (e.g., too much force limits motion of the tissue).

Referring now back to FIG. 1, optionally, at 118, the code implementableby the processors may identify regions of fibrotic tissue within thepatient. The identified fibrotic regions may be mapped to the displayedanatomical images of the patient, for example, marked by adistinguishable color from non-fibrotic tissue.

In one example, the fibrotic regions may be avoided when positioning thecatheter for ablation (e.g., by manual observation and/or by codeautomatically generating a warning). In another example, non-fibroticregions between or in proximity to the fibrotic regions are identified(manually by the operator or automatically by code) for additionalablation, such as when the previous ablation has been incomplete.

Reference is now made to FIG. 7, which is a flowchart of a method foridentifying regions of fibrotic tissue, in accordance with someembodiments of the present invention.

At 702, the code may receive one or more measurements of dielectricand/or thermal parameter(s) of the tissue in proximity to or of thetarget tissue, for example, impedance (e.g., complex impedance) and/orconductance.

Each measurement may be associated with the position of the distal endof the catheter when the measurement is obtained.

The measurements may be obtained from one or more electrodes and/orsensors of the physical catheter, for example, at the distal end of thecatheter.

At 704, multiple measurements may be performed at multiple locations inproximity to the target tissue. For example, the measuring catheter isdisplaced (e.g., manually by the operator or automatically by a robot)along the surface of the tissue, to cover a desired area.

At 706, the code may analyze the measurement associated with one or moreof the locations to identify an electric and/or thermal tissue signatureindicative of one or more fibrotic tissue regions. For example, a bandof fibrotic tissue (e.g., due to a scar), a circular clump of fibrotictissue (e.g., due to a previous ablation), and/or an irregular shape(e.g., due to naturally occurring fibrosis). The analysis may be basedon the imaginary value of the measured impedance (e.g., when theelectric tissue signature includes impedance measurements).

At 708 the code may map the identified fibrotic tissue regions to thedataset. The dataset may be provided for visual presentation that maydistinguish the fibrotic regions, for example, by a different color. Thedataset including the fibrotic tissue regions may be provided as inputto the simulation, e.g., when ablation of the target tissue issimulated.

Reference is now made to FIG. 8A, which is a schematic of a catheter formeasuring one or more dielectric and/or thermal properties of tissueslocated within a narrow body region, for example a collapsed potentialtissue space, for example, lung tissue within the pleural space, or themyocardium from within the pericardial space (depicted as exemplary, butis to be understood as applying to other similar body regions such asthe pleural space), in accordance with some embodiments of the presentinvention. Catheter 800 is designed to physically isolate the parietalpericardium from the visceral pericardium region in proximity to thesensors measuring the dielectric and/or thermal properties. Catheter 800may measure the impedance and/or conductance of the myocardium. Themeasurements may be more accurate and/or more precise over othermethods, due to the isolation of the parietal pericardium, which mayreduce errors (e.g., due to interference) due to effects of other nearbytissues in contact with the parietal pericardium.

Catheter 800 may be used to collect real-time measurements of thedielectric and/or thermal properties of the myocardium during theprocedure, for improving the accuracy of the location of the catheterand/or other features, as described herein. Catheter 800 may beintegrated with system 200. Optionally, sensors 810 are in communicationwith sensor interface 226 of unit 202. Unit 202 may include code toreceive signals from the sensors and calculate the impedance and/orconductance of the myocardium. Alternatively or additionally, catheter800 is a separate system, with measurements of the myocardium beingmanually entered into system 200 via user interface 224.

Optionally, sensors 810 are designed to measure the impedance at two ormore frequencies, simultaneously and/or sequentially. For example, thesignal may be applied as an input into a first sensor 810 (e.g.,proximal sensor) and measured at a second (or additional) sensor 810(e.g., distal sensor). Sensors 810 may be designed to measure a firstfrequency in the range of about 20-100 kHz (e.g., about 40 kHz) and asecond frequency of about 1 MHz. There may be, for example, two sensors,or four sensors, or other numbers of sensors. Sensors 810 may bedesigned to include the real and/or imaginary components of theimpedance measurement.

Catheter 800 is illustrated within a pericardial space 802, which islocated between a parietal pericardium 804 (which is in contact withother organs and/or tissues, such as large blood vessels and the lungs),and a visceral pericardium 806 which overlies and is attached to amyocardium 808 of a heart of the patient. For completeness, anendocardium 814 is the inner layer of the heart wall, which may form theinner surface of the heart chamber.

Catheter 800 may be inserted into pericardial space 802, for example,over a guidewire and/or sheath, which may be deployed via a needlehaving lumen via a sub-xiphoid approach or other approaches.

Optionally, the distal end portion of catheter 800 is designed forexpansion within the pericardial space, for example, self-expansion(e.g, made from Nickel-Titanium or other memory metals), and/or balloonexpandable. Catheter 800 may be expanded from a first contracted statedin which the distal end portion is sized for delivery into thepericardial space, to a second expanded state, in which the sensorscontact the visceral pericardium and the isolation element physicallyisolates the region between the sensors from the parietal pericardium.The expansion may be based on shape and/or geometrical changes of theisolation element.

Catheter 800 may include spaced apart sensors 810 (e.g.,microelectrodes) disposed at a distal end portion thereof, for example,two sensors spaced apart along the length of the catheter. Sensors 810are designed to contact the visceral pericardium in contact with themyocardium of a heart. Sensors 810 are designed to measure one or moredielectric and/or thermal properties of a portion of the myocardium,such as the impedance and/or conduction.

Catheter 800 may include an isolation element 812 disposed at a distalend portion thereof. Isolation element 812 is designed to physicallyisolate a region of the parietal pericardium from contact with a regionof the visceral pericardium between sensors 810 in contact with thevisceral pericardium. Optionally, isolation element 812 is designed tophysically isolate a region of the parietal pericardium from contactwith a region of the visceral pericardium in near proximity around theplurality of sensors in contact with the visceral pericardium, forexample, a circle surrounding sensors 810.

Optionally, the isolation element is arranged to apply a contact forcebetween sensors 810 and the visceral pericardium, for example, by aspring link action, or a preset bias. The force urges sensors 810towards the parietal pericardium, which may stabilize and/or providesufficient contact to allow for precise measurements.

Optionally, isolation element 812 is a strut (or wire) arranged in a Ushape in the expanded state and straight in the contracted state.Sensors 810 may be disposed on the distal arms of the U, or in proximityto the U. The arc of the U is designed to urge the parietal pericardiumaway from the visceral pericardium to form the isolated region (e.g., asillustrated).

Reference is now made to FIG. 8B, which is another design of a catheter820 (corresponding to catheter 800) for measurement of one or moredielectric and/or thermal properties of the myocardium from within thepericardial space, in accordance with some embodiments of the presentinvention.

Catheter 820 may include multiple arcs 822 at a distal end thereof,arranged to form a dome-like 826 shape. Electrodes 810 may be positionedwithin dome 826, at the flat part thereof (which is designed to contactthe visceral pericardium), by extension legs 824. The curved portion ofdome 826 physically isolates the parietal pericardium from the visceralpericardium within the flat part of dome 826.

Reference is now made to FIG. 8C, which is another design of a catheter830 (corresponding to catheter 800) for measurement of one or moredielectric and/or thermal properties of the myocardium from within thepericardial space, in accordance with some embodiments of the presentinvention. Catheter 830 may include an expandable balloon 832.Electrodes 810 may be positioned on the outer surface of balloon 832.Expansion of balloon 832 may physically isolate the parietal pericardiumfrom the visceral pericardium.

Some alternatives and/or optional features are now described withreferences to the systems and/or methods described herein. Thealternatives and/or features may be executed by code stored in theprogram store, implementable by the processor of the computing unit. Itis noted that the terms probe and catheter are sometimesinterchangeable.

-   -   The method of FIG. 1 and/or system of FIG. 2 may improve the        accuracy of impedance localization of an indwelling probe (e.g.,        navigation system 236 for the catheter) that has at least one        conducting port (e.g., sensor and/or electrode) at a locatable        location. The localization system may transmit and receive        alternating current between ports (on the catheter and/or on        another intra-body catheter, and/or at an extra-body location,        e.g., body electrode patches), in one frequency or multiple        different frequencies, and/or at different times, in co-planar        direction (or approximately).

The localization may be performed on a probe (e.g., tool, catheter) withmultiple conducting ports with predefined distances between each port.The systems and/or methods described herein may locate each portseparately (optionally simultaneously or iteratively within a shortperiod of time that appears simultaneous), making multi-pole locationdetermination of the same probe. For example, tracked as in block 106.It is noted that the terms pole, port (e.g., conduction port), andelectrode are sometimes interchangeable, for example, Pole isinterchangeable with porti.

Optionally, the distances between the conducting ports is measuredand/or determined, for example, downloading the specification from aremote server (e.g., via a network connection), measured usingfluoroscopic measurements, and/or measured using a measuring device(e.g., ruler), and/or reading the catheter identification informationfrom a computer readable medium (e.g., stored on the catheter itself,stored on the connector, stored on the computing unit, and/or storedremotely).

The identification of other unique properties (e.g., frequency, size) ofthe catheter may be derived from the inter-pole distances. For example,the inter-pole distances are used to access a record of the catheter, todetermine the catheter model number. When the model number is known,other unique properties may be retrieved.

Based on the inter-pole distance, the location of each pole may bedetermined. The inter-pole distance may improve the accuracy of thelocation determination, for example, by correcting the determinedlocation of each pole according to the known inter-pole distance.

The location of the catheter may be calibrated based on the inter-poledistance and/or based on the corrected coordinates according to theinter-pole distance, e.g., based on comparison of the calculateddistance from run-time measurements to the known distance.

The code may activate the poles on the catheter and/or external poles(or another intra-body catheter, and/or extra-body poles), to transmitmultiple radio waves from one or more of the poles for reception at oneor more other poles. The relationship between the transmitted andreceived signals may be analyzed to determine characteristics of thecatheter. The analysis may determine a baseline signature (e.g.,relative or absolute), which serves for comparison to trace and/ormonitor the multi-pole interaction with surrounding tissues and/or radiosignals during the procedure, as described herein.

It is expected that during the life of a patent maturing from thisapplication many relevant navigation systems and intra-body catheterswill be developed and the scope of the terms navigation system andcatheter are intended to include all such new technologies a priori.

As used herein the term “about” refers to ±10%.

The terms “comprises”, “comprising”, “includes”, “including”, “having”and their conjugates mean “including but not limited to”.

The term “consisting of” means “including and limited to”.

The term “consisting essentially of” means that the composition, methodor structure may include additional ingredients, steps and/or parts, butonly if the additional ingredients, steps and/or parts do not materiallyalter the basic and novel characteristics of the claimed composition,method or structure.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise. For example,the term “a compound” or “at least one compound” may include a pluralityof compounds, including mixtures thereof.

Throughout this application, various embodiments of this invention maybe presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Accordingly, the description of a range should be consideredto have specifically disclosed all the possible subranges as well asindividual numerical values within that range. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numberswithin that range, for example, 1, 2, 3, 4, 5, and 6. This appliesregardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to includeany cited numeral (fractional or integral) within the indicated range.The phrases “ranging/ranges between” a first indicate number and asecond indicate number and “ranging/ranges from” a first indicate number“to” a second indicate number are used herein interchangeably and aremeant to include the first and second indicated numbers and all thefractional and integral numerals therebetween.

As used herein the term “method” refers to manners, means, techniquesand procedures for accomplishing a given task including, but not limitedto, those manners, means, techniques and procedures either known to, orreadily developed from known manners, means, techniques and proceduresby practitioners of the chemical, pharmacological, biological,biochemical and medical arts.

As used herein, the term “treating” includes abrogating, substantiallyinhibiting, slowing or reversing the progression of a condition,substantially ameliorating clinical or aesthetical symptoms of acondition or substantially preventing the appearance of clinical oraesthetical symptoms of a condition.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention. To the extent thatsection headings are used, they should not be construed as necessarilylimiting.

What is claimed is:
 1. A system for tracking a position of an intra-bodycatheter, comprising: an output interface for communicating with adisplay; an electrode interface for communicating with a plurality ofphysical electrodes on a distal end portion of a physical catheterdesigned for intra-body navigation; a program store storing code; and aprocessor coupled to the output interface, the electrode interface, andthe program store for implementing the stored code, the code comprising:code to receive measurements of a plurality of electrical fields appliedwithin the body portion, measured by the plurality of physicalelectrodes; code to calculate and physically track coordinates of theposition of the distal end of the physical catheter within the physicalbody portion of the patient according to the received measurements ofthe plurality of electric fields measured by the plurality of physicalelectrodes; code to register between the physically tracked coordinates,indicative of position of the distal end of the physical catheter, andsimulation coordinates, indicative of simulated position of the distalend of the physical catheter, the simulation coordinates generatedaccording to a simulation of a simulated catheter within a simulation ofthe body of the patient; code to compute corrected physically trackedcoordinates by correcting the physically tracked coordinates obtainedaccording to the registered simulation coordinates; and code to transmitthe corrected physically tracked coordinates to the output interface. 2.The system of claim 1, further comprising: an imaging interface forcommunicating with an imaging modality that acquires a dataset ofanatomical imaging data of a patient; wherein the processor is furthercoupled to the imaging interface; code to receive the dataset, andassociate at least one dielectric parameter value corresponding todifferent tissues of the anatomical imaging data of the dataset, whereinthe at least one dielectric parameter value represents an initialestimated value; and code to generate the simulation that trackscoordinates of a position of the simulated catheter within the datasetrepresenting the body portion according to simulated application of aplurality of electrical fields within the body portion and measurementsof the electrical field performed by a plurality of electrodes at adistal portion of the catheter.
 3. The system of claim 1, furthercomprising a connector having a first port for connecting to thephysical catheter, a second port for connecting to a control unitassociated with the physical catheter, and a third port for connectingto the electrode interface, the connector including circuitry tointercept signal transmission between the physical catheter and thecontrol unit and transmit the intercepted signals to the electrodeinterface without interfering with the signal transmission between thephysical catheter and the control unit.
 4. The system of claim 2,wherein the dataset includes three dimensional (3D) anatomical imagingdata acquired by at least one of a CT and an MRI.
 5. A system fortracking a position of an intra-body catheter, comprising: an outputinterface for communication with a display; an input interface forcommunication with a navigation system; a program store storing code;and a processor coupled to the input interface, the output interface,and the program store for implementing the stored code, the codecomprising: code to receive, via the input interface, coordinates of acatheter within a body of a patient, the coordinates computed accordingto measurements of applied electric fields by a plurality of physicalelectrodes; code to compute corrected physically tracked coordinates bycorrecting the coordinates according to a simulation of the catheterwithin the body, the simulation being based on a dielectric mapincluding acquired anatomical imaging data of the patient and at leastone dielectric parameter value corresponding to one or more differenttissues identified within the anatomical imaging data; and code toprovide the corrected coordinates to the output interface forpresentation on the display.